Gene Summary

Gene:S100A10; S100 calcium binding protein A10
Aliases: 42C, P11, p10, GP11, ANX2L, CAL1L, CLP11, Ca[1], ANX2LG
Summary:The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in exocytosis and endocytosis. [provided by RefSeq, Jul 2008]
Databases:OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene
Protein:protein S100-A10
Source:NCBIAccessed: 06 August, 2015


What does this gene/protein do?
Show (6)

Cancer Overview

Research Indicators

Publications Per Year (1990-2015)
Graph generated 06 August 2015 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Western Blotting
  • Transcriptional Activation
  • Messenger RNA
  • Esophageal Cancer
  • Tumor Markers
  • Radiation-Sensitizing Agents
  • Cancer Gene Expression Regulation
  • Squamous Cell Carcinoma
  • Down-Regulation
  • S100 calcium binding protein A10
  • DNA Methylation
  • Cerebellar Neoplasms
  • Chromosome 1
  • Lung Cancer
  • Stomach Cancer
  • Cell Proliferation
  • Membrane Proteins
  • DNA Primers
  • Gene Expression Regulation
  • Calcium-Binding Proteins
  • Immunohistochemistry
  • Neoplasm Proteins
  • src-Family Kinases
  • Polymerase Chain Reaction
  • Fibrinolysin
  • Skin Cancer
  • Oncogene Fusion Proteins
  • U937 Cells
  • Base Sequence
  • Signal Transduction
  • Neoplasm Invasiveness
  • Gene Expression
  • Immunoenzyme Techniques
  • Gene Expression Profiling
  • Translocation
  • Oligonucleotide Array Sequence Analysis
  • Annexin A2
  • S100 Proteins
  • Vault Ribonucleoprotein Particles
Tag cloud generated 06 August, 2015 using data from PubMed, MeSH and CancerIndex

Specific Cancers (5)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: S100A10 (cancer-related)

Zhang Q, Zhu M, Cheng W, et al.
Downregulation of 425G>a variant of calcium-binding protein S100A14 associated with poor differentiation and prognosis in gastric cancer.
J Cancer Res Clin Oncol. 2015; 141(4):691-703 [PubMed] Related Publications
PURPOSE: Altered level of S100 calcium-binding proteins is involved in tumor development and progression. However, their role in gastric cancer (GC) is not well documented. We investigated the expression pattern of S100 proteins and differentiation or prognosis as well as possible mechanisms in GC.
METHODS: RT-PCR, Western blot analysis, and immunohistochemistry were used to determine the mRNA and protein expression of S100 family genes in GC. The polymorphisms of promoter and 5'-UTR of S100A14 gene were identified and related to luciferase reporter gene activity. Association of S100A14 expression with clinicopathologic features and survival in GC was analyzed.
RESULTS: We detected upregulated S100A2, S100A6, S100A10, and S100A11 expression and downregulated S100P and S100B expression in GC. Particularly, we detected differential mRNA and protein expression of S100A14 in GC cell lines and primary tumors. Furthermore, S100A14 expression change was related to a differentiated GC phenotype, with an expression in 31/40 (77.5 %) samples of well-differentiated tumors and 29/85 (34.1 %) samples of poorly differentiated tumors (P < 0.001). Moreover, 5-year survival was better in GC cases with positive than negative S100A14 level (P = 0.02). The genetic variant 425G>A on the 5'-UTR of S100A14 was associated with reduced S100A14 expression in GC cells.
CONCLUSION: Decreased expression of S100A14 with presence of its genetic variant 425G>A may be associated with an undifferentiated phenotype and poor prognosis in GC.

Andey T, Marepally S, Patel A, et al.
Cationic lipid guided short-hairpin RNA interference of annexin A2 attenuates tumor growth and metastasis in a mouse lung cancer stem cell model.
J Control Release. 2014; 184:67-78 [PubMed] Related Publications
The role of side populations (SP) or cancer stem-like cells (CSC) in promoting the resistance phenotype presents a viable anticancer target. Human-derived H1650 SP cells over-express annexin A2 (AnxA2) and SOX2, and are resistant to conventional cytotoxic chemotherapeutics. AnxA2 and SOX2 bind to proto-oncogenes, c-Myc and c-Src, and AnxA2 forms a functional heterotetramer with S100A10 to promote tumor motility. However, the combined role of AnxA2, S100A10 and SOX2 in promoting the resistant phenotype of SP cells has not been investigated. In the current studies, we examined for the first time a possible role of AnxA2 in regulating SA100A10 and SOX2 in promoting a resistant phenotype of lung tumors derived from H1650 SP cells. The resistance of H1650 SP cells to chemotherapy compared to H1650 MP cells was investigated by cell viability studies. A short hairpin RNA targeting AnxA2 (shAnxA2) was formulated in a liposomal (cationic ligand-guided, CLG) carrier and characterized for size, charge and entrapment and loading efficiencies; CLG carrier uptake by H1650 SP cells was demonstrated by fluorescence microscopy, and knockdown of AnxA2 confirmed by qRT-PCR and Western blot. Targeting of xenograft and orthotopic lung tumors was demonstrated with fluorescent (DiR) CLG carriers in mice. The therapeutic efficacy of CLG-AnxA2, compared to that of placebo, was investigated after 2 weeks of treatment in terms of tumor weights and tumor burden in vivo. Compared to mixed population cells, H1650 SP cells showed exponential resistance to docetaxel (15-fold), cisplatin (13-fold), 5-fluorouracil (31-fold), camptothecin (7-fold), and gemcitabine (16-fold). CLG carriers were nanoparticulate (199nm) with a slight positive charge (21.82mV); CLG-shAnx2 was of similar size (217nm) with decreased charge (12.11mV), and entrapment and loading efficiencies of 97% and 6.13% respectively. Fluorescence microscopy showed high uptake of CLG-shAnxA2 in H1650 SP cells after 2h resulting in a 6-fold reduction in AnxA2 mRNA expression and 92% decreased protein expression. Fluorescence imaging confirmed targeting of tumors and lungs by DiR-CLG carriers with sustained localization up to 4h in mice. CLG-shAnxA2 treatment of mice significantly reduced the weights of lung tumors derived from H1650 SP cells and tumor burden was reduced to only 19% of controls. The loss in tumor weights in response to CLG-shAnxA2 was associated with a significant loss in the relative levels of AnxA2, SOX2, total β-catenin and S100A10, both at the RNA and protein levels. These results suggest the intriguing possibility that AnxA2 may directly or indirectly regulate relative levels of β-catenin, S100A10 and SOX2, and that the combination of these factors may contribute to the resistant phenotype of H1650 SP cells. Thus down-regulating AnxA2 using RNAi methods may provide a useful method for targeting cancer stem cells and help advance therapeutic efficacy against lung cancers.

Panagopoulos I, Brandal P, Gorunova L, et al.
Novel CSF1-S100A10 fusion gene and CSF1 transcript identified by RNA sequencing in tenosynovial giant cell tumors.
Int J Oncol. 2014; 44(5):1425-32 [PubMed] Free Access to Full Article Related Publications
RNA-sequencing was performed on three tenosynovial giant cell tumors (TSGCT) in an attempt to elicit more information on the mechanisms of CSF1 expression in this tumor type. A novel CSF1-S100A10 fusion gene was found in a TSGCT that carried the translocation t(1;1)(q21;p11) as the sole karyotypic abnormality. In this fusion gene, the part of CSF1 coding for the CSF1 protein (exons 1-8 in sequences with accession nos. NM_000757 and NM_172212) is fused to the 3'-part of S100A10. Since the stop codon TAG of CSF1 is present in it, the CSF1-S100A10 fusion gene's predominant consequence seems to be the replacement of the 3'-untranslated region (UTR) of CSF1 (exon 9; nt 2092-4234 in sequence with accession no. NM_000757 or nt 2092-2772 in NM_172212) by the 3'-end of S100A10 (exon 3; nt 641-1055 in sequence with accession no. NM_002966). In the other two TSGCT, a novel CSF1 transcript was detected, the same in both tumors. Similar to the occurrence in the CSF1-S100A10 fusion gene, the novel CSF1 transcript 3'-UTR is replaced by a new exon located ~48 kb downstream of CSF1 and 11 kb upstream of AHCYL1. Although only 3 TSGCT were available for study, the finding in all of them of a novel CSF1-S100A10 fusion gene or CSF1 transcript indicates the existence of a common pathogenetic theme in this tumor type: the replacement of the 3'-UTR of CSF1 with other sequences.

Fujishiro H, Ohashi T, Takuma M, Himeno S
Down-regulation of S100A9 and S100A10 in manganese-resistant RBL-2H3 cells.
J Toxicol Sci. 2013; 38(5):753-7 [PubMed] Related Publications
Exposure to excess amounts of manganese causes toxic effects, including neurological symptoms such as Parkinsonism. However, endogenous factors involved in the protection against manganese toxicity remain unclear. Previously, we showed that rat basophilic leukemia RBL-2H3 cells are highly sensitive to MnCl₂ compared with other rat cell lines. To identify the genes involved in resistance to manganese toxicity, two lines of Mn-resistant cells showing resistance to 300 µM MnCl₂ (RBL-Mnr300) and 1200 µM MnCl₂ (RBL-Mnr1200) were developed from RBL-2H3 cells by a stepwise increase in MnCl₂ concentration in the medium. Microarray analyses were carried out to compare gene expression between parental RBL-2H3 cells and RBL-Mnr300 or RBL-Mnr1200 cells. Five genes exhibited more than 10-fold up-regulation in both RBL-Mnr300 and RBL-Mnr1200 cells, and 24 genes exhibited less than 0.1-fold down-regulation in both Mn-resistant cell lines. The S100a9 and S100a10 genes, encoding the calcium-binding S100A9 and S100A10 proteins, respectively, were found among the three most down-regulated genes in both Mn-resistant cell lines. The marked decreases in mRNA levels of S100a9 and S100a10 were confirmed by real-time RT-PCR analyses. Further characterization and comparison of these Mn-resistant cells may enable the identification of novel genes that play important roles in the modification of manganese toxicity.

Zheng X, Naiditch J, Czurylo M, et al.
Differential effect of long-term drug selection with doxorubicin and vorinostat on neuroblastoma cells with cancer stem cell characteristics.
Cell Death Dis. 2013; 4:e740 [PubMed] Free Access to Full Article Related Publications
Numerous studies have confirmed that cancer stem cells (CSCs) are more resistant to chemotherapy; however, there is a paucity of data exploring the effect of long-term drug treatment on the CSC sub-population. The purpose of this study was to investigate whether long-term doxorubicin treatment could expand the neuroblastoma cells with CSC characteristics and histone acetylation could affect stemness gene expression during the development of drug resistance. Using n-myc amplified SK-N-Be(2)C and non-n-myc amplified SK-N-SH human neuroblastoma cells, our laboratory generated doxorubicin-resistant cell lines in parallel over 1 year; one cell line intermittently treated with the histone deacetylase inhibitor (HDACi) vorinostat and the other without exposure to HDACi. Cells' sensitivity to chemotherapeutic drugs, the ability to form tumorspheres, and capacity for in vitro invasion were examined. Cell-surface markers and side populations (SPs) were analyzed using flow cytometry. Differentially expressed stemness genes were identified through whole genome analysis and confirmed with real-time PCR. Our results indicated that vorinostat increased the sensitivity of only SK-N-Be(2)C-resistant cells to chemotherapy, made cells lose the ability to form tumorspheres, and reduced in vitro invasion and the SP percentage. CD133 was not enriched in doxorubicin-resistant or vorinostat-treated doxorubicin-resistant cells. Nine stemness-linked genes (ABCB1, ABCC4, LMO2, SOX2, ERCC5, S100A10, IGFBP3, TCF3, and VIM) were downregulated in vorinostat-treated doxorubicin-resistant SK-N-Be(2)C cells relative to doxorubicin-resistant cells. A sub-population of cells with CSC characteristics is enriched during prolonged drug selection of n-myc amplified SK-N-Be(2)C neuroblastoma cells. Vorinostat treatment affects the reversal of drug resistance in SK-N-Be(2)C cells and may be associated with downregulation of stemness gene expression. This work may be valuable for clinicians to design treatment protocols specific for different neuroblastoma patients.

Spijkers-Hagelstein JA, Mimoso Pinhanços S, Schneider P, et al.
Src kinase-induced phosphorylation of annexin A2 mediates glucocorticoid resistance in MLL-rearranged infant acute lymphoblastic leukemia.
Leukemia. 2013; 27(5):1063-71 [PubMed] Related Publications
MLL-rearranged infant acute lymphoblastic leukemia (ALL) (<1 year of age) are frequently resistant to glucocorticoids, like prednisone and dexamethasone. As poor glucocorticoid responses are strongly associated with therapy failure, overcoming glucocorticoid resistance may be a crucial step towards improving prognosis. Unfortunately, the mechanisms underlying glucocorticoid resistance in MLL-rearranged ALL largely remain obscure. We here defined a gene signature that accurately discriminates between prednisolone-resistant and prednisolone-sensitive MLL-rearranged infant ALL patient samples, demonstrating that, among other genes, high-level ANXA2 is associated with prednisolone resistance in this type of leukemia. Further investigation demonstrated that the underlying factor of this association was the presence of Src kinase-induced phosphorylation (activation) of annexin A2, a process requiring the adapter protein p11 (encoded by human S100A10). shRNA-mediated knockdown of either ANXA2, FYN, LCK or S100A10, all led to inhibition of annexin A2 phosphorylation and resulted in marked sensitization to prednisolone. Likewise, exposure of prednisolone-resistant MLL-rearranged ALL cells to different Src kinase inhibitors exerting high specificity towards FYN and/or LCK had similar effects. In conclusion, we here present a novel mechanism of prednisolone resistance in MLL-rearranged leukemias, and propose that inhibition of annexin A2 phosphorylation embodies a therapeutic strategy for overcoming resistance to glucocorticoids in this highly aggressive type of leukemia.

Johnson H, Del Rosario AM, Bryson BD, et al.
Molecular characterization of EGFR and EGFRvIII signaling networks in human glioblastoma tumor xenografts.
Mol Cell Proteomics. 2012; 11(12):1724-40 [PubMed] Free Access to Full Article Related Publications
Glioblastoma multiforme (GBM) is a malignant primary brain tumor with a mean survival of 15 months with the current standard of care. Genetic profiling efforts have identified the amplification, overexpression, and mutation of the wild-type (wt) epidermal growth factor receptor tyrosine kinase (EGFR) in ≈ 50% of GBM patients. The genetic aberration of wtEGFR is frequently accompanied by the overexpression of a mutant EGFR known as EGFR variant III (EGFRvIII, de2-7EGFR, ΔEGFR), which is expressed in 30% of GBM tumors. The molecular mechanisms of tumorigenesis driven by EGFRvIII overexpression in human tumors have not been fully elucidated. To identify specific therapeutic targets for EGFRvIII driven tumors, it is important to gather a broad understanding of EGFRvIII specific signaling. Here, we have characterized signaling through the quantitative analysis of protein expression and tyrosine phosphorylation across a panel of glioblastoma tumor xenografts established from patient surgical specimens expressing wtEGFR or overexpressing wtEGFR (wtEGFR+) or EGFRvIII (EGFRvIII+). S100A10 (p11), major vault protein, guanylate-binding protein 1(GBP1), and carbonic anhydrase III (CAIII) were identified to have significantly increased expression in EGFRvIII expressing xenograft tumors relative to wtEGFR xenograft tumors. Increased expression of these four individual proteins was found to be correlated with poor survival in patients with GBM; the combination of these four proteins represents a prognostic signature for poor survival in gliomas. Integration of protein expression and phosphorylation data has uncovered significant heterogeneity among the various tumors and has highlighted several novel pathways, related to EGFR trafficking, activated in glioblastoma. The pathways and proteins identified in these tumor xenografts represent potential therapeutic targets for this disease.

Giráldez MD, Lozano JJ, Cuatrecasas M, et al.
Gene-expression signature of tumor recurrence in patients with stage II and III colon cancer treated with 5'fluoruracil-based adjuvant chemotherapy.
Int J Cancer. 2013; 132(5):1090-7 [PubMed] Related Publications
Although receiving adjuvant chemotherapy after radical surgery, a disappointing proportion of patients with colorectal cancer will develop tumor recurrence. Probability of relapse is currently predicted from pathological staging, there being a need for additional markers to further select high-risk patients. This study was aimed to identify a gene-expression signature to predict tumor recurrence in patients with Stages II and III colon cancer treated with 5'fluoruracil (5FU)-based adjuvant chemotherapy. Two-hundred and twenty-eight patients diagnosed with Stages II-III colon cancer and treated with surgical resection and 5FU-based adjuvant chemotherapy were included. RNA was extracted from formalin-fixed, paraffin-embedded tissue samples and expression of 27 selected candidate genes was analyzed by RT-qPCR. A tumor recurrence predicting model, including clinico-pathological variables and gene-expression profiling, was developed by Cox regression analysis and validated by bootstrapping. The regression analysis identified tumor stage and S100A2 and S100A10 gene expression as independently associated with tumor recurrence. The risk score derived from this model was able to discriminate two groups with a highly significant different probability of tumor recurrence (HR, 2.75; 95%CI, 1.71-4.39; p = 0.0001), which it was maintained when patients were stratified according to tumor stage. The algorithm was also able to distinguish two groups with different overall survival (HR, 2.68; 95%CI, 1.12-6.42; p = 0.03). Identification of a new gene-expression signature associated with a high probability of tumor recurrence in patients with Stages II and III colon cancer receiving adjuvant 5FU-based chemotherapy, and its combination in a robust, easy-to-use and reliable algorithm may contribute to tailor treatment and surveillance strategies.

Elsner M, Rauser S, Maier S, et al.
MALDI imaging mass spectrometry reveals COX7A2, TAGLN2 and S100-A10 as novel prognostic markers in Barrett's adenocarcinoma.
J Proteomics. 2012; 75(15):4693-704 [PubMed] Related Publications
To characterize proteomic changes found in Barrett's adenocarcinoma and its premalignant stages, the proteomic profiles of histologically defined precursor and invasive carcinoma lesions were analyzed by MALDI imaging MS. For a primary proteomic screening, a discovery cohort of 38 fresh frozen Barrett's adenocarcinoma patient tissue samples was used. The goal was to find proteins that might be used as markers for monitoring cancer development as well as for predicting regional lymph node metastasis and disease outcome. Using mass spectrometry for protein identification and validating the results by immunohistochemistry on an independent validation set, we could identify two of 60 differentially expressed m/z species between Barrett's adenocarcinoma and the precursor lesion: COX7A2 and S100-A10. Furthermore, among 22 m/z species that are differentially expressed in Barrett's adenocarcinoma cases with and without regional lymph node metastasis, one was identified as TAGLN2. In the validation set, we found a correlation of the expression levels of COX7A2 and TAGLN2 with a poor prognosis while S100-A10 was confirmed by multivariate analysis as a novel independent prognostic factor in Barrett's adenocarcinoma. Our results underscore the high potential of MALDI imaging for revealing new biologically significant molecular details from cancer tissues which might have potential for clinical application. This article is part of a Special Issue entitled: Translational Proteomics.

Fenouille N, Grosso S, Yunchao S, et al.
Calpain 2-dependent IκBα degradation mediates CPT-11 secondary resistance in colorectal cancer xenografts.
J Pathol. 2012; 227(1):118-29 [PubMed] Related Publications
CPT-11 (irinotecan), the first-line chemotherapy for advanced stage colorectal cancer, remains inactive in about half of patients (primary chemoresistance) and almost all initial responders develop secondary resistance after several courses of treatment (8 months on average). Nude mice bearing HT-29 colon cancer xenografts were treated with CPT-11 and/or an NF-κB inhibitor for two courses. We confirm that NF-κB inhibition potentiated CPT-11 anti-tumoural effect after the first course of treatment. However, tumours grew again at the end of the second course of treatment, generating resistant tumours. We observed an increase in the basal NF-κB activation in resistant tumours and in two resistant sublines, either obtained from resistant HT-29 tumours (HT-29R cells) or generated in vitro (RSN cells). The decrease of NF-κB activation in HT-29R and RSN cells by stable transfections with the super-repressor form of IκBα augmented their sensitivity to CPT-11. Comparing gene expression profiles of HT-29 and HT-29R cells, we identified the S100A10/Annexin A2 complex and calpain 2 as over-expressed potential NF-κB inducers. SiRNA silencing of calpain 2 but not of S100A10 and/or annexin A2, resulted in a decrease in NF-κB activation, an increase in cellular levels of IκBα and a partial restoration of the CPT-11 sensitivity in both HT-29R and RSN cells, suggesting that calpain 2-dependent IκBα degradation mediates CPT-11 secondary resistance. Thus, targeted therapies directed against calpain 2 may represent a novel strategy to enhance the anti-cancer efficacy of CPT-11.

Li J, Riau AK, Setiawan M, et al.
S100A expression in normal corneal-limbal epithelial cells and ocular surface squamous cell carcinoma tissue.
Mol Vis. 2011; 17:2263-71 [PubMed] Free Access to Full Article Related Publications
PURPOSE: To study the expression and cellular distribution of multiple S100A genes and proteins in normal corneal-limbal epithelium and ocular surface squamous cell carcinoma (SCC) tissue.
METHODS: Normal corneal-limbal tissue was obtained from the Lions Eye Bank, Tampa, FL. Ocular surface SCC tissues were excised from patients undergoing surgery at Singapore National Eye Centre. S100A mRNA expression was measured by quantitative PCR. S100 protein distribution was determined by immunofluorescent staining analysis.
RESULTS: Twelve S100 mRNAs were identified in human corneal and limbal epithelial cells. S100A2, A6, A8, A9, A10, and A11 mRNA was expressed at high level, while S100A1, A3, A4, A5, A6, A7, and A12 mRNA expression was low. The intracellular localization of S100A2, A6, A8, A9, A10 and A11 protein was determined in normal corneal-limbal and SCC tissues. S100A2 and S100A10 proteins were enriched in basal limbal epithelial cells of the normal tissue. S100A8 and S100A9 were found only at the surface of peripheral corneal and limbal epithelium. S100A6 was uniformly found at the plasma membrane of corneal and limbal epithelial cells. S100A11 was found at the supralayer limbal epithelial cells adjacent to the conjunctiva. SCC tissue showed typical pathological changes with expression of cytokeartin (CK) 14 and CK4 in the epithelial cells. All SCC epithelial cells were positive of S100A2, S100A10, S100A6 and S100A11 staining. Intracellular staining of S100A8 and S100A9 was found in several layers of SCC epithelium. Expression of S100A2 and S100A10 decreased dramatically in cultured limbal epithelial cells with increased passaging, which was accompanied by a small increase of S100A9 mRNA, with no changes of S100A8 gene expression. Serum and growth hormone depletion of the culture serum caused a small reduction of S100A2 and S100A10 gene expression, which was accompanied by a small increase of S100A9 mRNA while no changes of S100A8 expression was measured.
CONCLUSIONS: Normal corneal and limbal epithelial cells express a broad spectrum of S100 genes and proteins. Ocular surface SCC express high levels of S100A2, S100A10, S100A8 and S100A9 proteins. The expression of S100A2 and S100A10 is associated with limbal epithelial cell proliferation and differentiation.

Huang JC, Zhao PC, Zhang HZ, Wang H
A proteomical study on the radiosensitized target molecules of fuzheng zengxiao formula in pulmonary adenocarcinoma nude mice model.
J Tradit Chin Med. 2011; 31(1):3-6 [PubMed] Related Publications
OBJECTIVE: To investigate the radiosensitized target of Fuzheng Zengxiao Formula.
METHODS: The pulmonary adenocarcinoma (PAa) nude mice of tumor transplantation model were prepared and divided into four groups: Group I (blank control group, n = 10), Group II (simple radiotherapy group, n = 10), Group III (radiotherapy plus Fuzheng Zengxiao Formula, n = 10) and Group IV (radiotherapy plus metronidazole, n = 10). Radiation of X-rays was given to the tumors in Group I, II and III when they were averagely about 1 centimetre in diameter. 23 hours later, the tumors were taken, the total proteins were extracted, and the protein contents were determined. The proteins were isolated with two dimensional gel electrophoresis, and the differentially expressed proteins were analyzed with mass spectrometry and identified by protein database.
RESULTS: Six significant proteins, including apolipoprotein E, ceratin75, S100A9, cyclophilin A, S100A10 and hemoglobin, were determined. Compared with Group I, apolipoprotein E and ceratin75 highly expressed in the Group II; compared with Group II, S100A9, cyclophilin A and hemoglobin had high expression in the Group III; compared with Group II, S100A9, cyclophilin A, S100A10 and hemoglobin had high expression in the Group IV; compared with Group IV, S100A9 and S100A10 had low expression and hemoglobin had high expression in Group III.
CONCLUSION: The radiosensitization of Fuzheng Zengxiao Formula is related with the improvement of hypoxia state; and possibly S100A9 and cyclophilin A are the target proteins of Fuzheng Zengxiao Formula in radiosensitization.

Yang X, Popescu NC, Zimonjic DB
DLC1 interaction with S100A10 mediates inhibition of in vitro cell invasion and tumorigenicity of lung cancer cells through a RhoGAP-independent mechanism.
Cancer Res. 2011; 71(8):2916-25 [PubMed] Free Access to Full Article Related Publications
The DLC1 gene encodes a Rho GTPase-activating protein (RhoGAP) that functions as a tumor suppressor in several common human cancers. The multidomain structure of DLC1 enables interaction with a number of other proteins. Here we report that the proinflammatory protein S100A10 (also known as p11), a key cell surface receptor for plasminogen which regulates pericellular proteolysis and tumor cell invasion, is a new binding partner of DLC1 in human cells. We determined that the 2 proteins colocalize in the cell cytoplasm and that their binding is mediated by central sequences in the central domain of DLC1 and the C-terminus of S100A10. Because the same S100A10 sequence also mediates binding to Annexin 2, we found that DLC1 competed with Annexin 2 for interaction with S100A10. DLC1 binding to S100A10 did not affect DLC1's RhoGAP activity, but it decreased the steady-state level of S100A10 expression in a dose-dependent manner by displacing it from Annexin 2 and making it accessible to ubiquitin-dependent degradation. This process attenuated plasminogen activation and resulted in inhibition of in vitro cell migration, invasion, colony formation, and anchorage-independent growth of aggressive lung cancer cells. These results suggest that a novel GAP-independent mechanism contributes to the tumor suppressive activity of DLC1, and highlight the importance and complexity of protein-protein interactions involving DLC1 in certain cancers.

Shimizu Y, Fujishiro H, Matsumoto K, et al.
Chronic exposure to arsenite induces S100A8 and S100A9 expression in rat RBL-2H3 mast cells.
J Toxicol Sci. 2011; 36(1):135-9 [PubMed] Related Publications
To investigate the effects of chronic exposure to arsenite on the gene expression profiles of mast cells, microarray analysis was performed on rat basophilic leukemia RBL-2H3 cells exposed to arsenite for 28 days. Upregulated genes include calcium-binding S100 proteins such as S100A9, S100A10, S100A6, and S100A13, and granzymes B and C. Among S100 proteins, S100A9 showed the highest expression (8.62-fold of untreated cells) after 4-weeks of exposure to arsenite. As S100A8 and S100A9 comprise a heterodimer called calprotectin, and are implicated in the development of atherosclerosis and cancer, mRNA levels of both S100A8 and S100A9 were analyzed. The results demonstrated that exposure of RBL-2H3 cells to arsenite for a few weeks induces marked increases in mRNA levels of S100A8 and S100A9.

McKiernan E, McDermott EW, Evoy D, et al.
The role of S100 genes in breast cancer progression.
Tumour Biol. 2011; 32(3):441-50 [PubMed] Related Publications
The S100 gene family encode low molecular weight proteins implicated in cancer progression. In this study, we analyzed the expression of four S100 genes in one cohort of patients with breast cancer and 16 S100 genes in a second cohort. In both cohorts, the expression of S100A8 and S1009 mRNA level was elevated in high-grade compared to low-grade tumors and in estrogen receptor-negative compared to estrogen receptor-positive tumors. None of the S100 transcripts investigated were significantly associated with the presence of lymph node metastasis. Notably, multiple S100 genes, including S100A1, S100A2, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, and S100A14 were upregulated in basal-type breast cancers compared to non-basal types. Using Spearman's correlation analysis, several S100 transcripts correlated significantly with each other, the strongest correlation has been found between S100A8 and S100A9 (r = 0.889, P < 0.001, n = 295). Of the 16 S100 transcripts investigated, only S100A11 and S100A14 were significantly associated with patient outcome. Indeed, these two transcripts predicted outcome in the cohort of patients that did not receive systemic adjuvant therapy. Based on our findings, we conclude that the different S100 genes play varying roles in breast cancer progression. Specific S100 genes are potential targets for the treatment of basal-type breast cancers.

Romanuik TL, Wang G, Morozova O, et al.
LNCaP Atlas: gene expression associated with in vivo progression to castration-recurrent prostate cancer.
BMC Med Genomics. 2010; 3:43 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: There is no cure for castration-recurrent prostate cancer (CRPC) and the mechanisms underlying this stage of the disease are unknown.
METHODS: We analyzed the transcriptome of human LNCaP prostate cancer cells as they progress to CRPC in vivo using replicate LongSAGE libraries. We refer to these libraries as the LNCaP atlas and compared these gene expression profiles with current suggested models of CRPC.
RESULTS: Three million tags were sequenced using in vivo samples at various stages of hormonal progression to reveal 96 novel genes differentially expressed in CRPC. Thirty-one genes encode proteins that are either secreted or are located at the plasma membrane, 21 genes changed levels of expression in response to androgen, and 8 genes have enriched expression in the prostate. Expression of 26, 6, 12, and 15 genes have previously been linked to prostate cancer, Gleason grade, progression, and metastasis, respectively. Expression profiles of genes in CRPC support a role for the transcriptional activity of the androgen receptor (CCNH, CUEDC2, FLNA, PSMA7), steroid synthesis and metabolism (DHCR24, DHRS7, ELOVL5, HSD17B4, OPRK1), neuroendocrine (ENO2, MAOA, OPRK1, S100A10, TRPM8), and proliferation (GAS5, GNB2L1, MT-ND3, NKX3-1, PCGEM1, PTGFR, STEAP1, TMEM30A), but neither supported nor discounted a role for cell survival genes.
CONCLUSIONS: The in vivo gene expression atlas for LNCaP was sequenced and support a role for the androgen receptor in CRPC.

Zhang J, Guo B, Zhang Y, et al.
Silencing of the annexin II gene down-regulates the levels of S100A10, c-Myc, and plasmin and inhibits breast cancer cell proliferation and invasion.
Saudi Med J. 2010; 31(4):374-81 [PubMed] Related Publications
OBJECTIVE: To explore the roles of annexin II in breast cancer progression, and to study the effect of annexin II on breast cancer cell proliferation and invasion.
METHODS: This study was conducted in the Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China from December 2006 to January 2009. First, we employed Western blot and reverse transcriptase polymerase chain reaction to detect the expression of annexin II and S100A10 in a panel of well-characterized human breast cancer cell lines, and investigated the localization of annexin II and S100A10 by use of immunofluorescence. We then silenced the expression of annexin II in MDA-MB-435s, which was found to over express annexin II, using the chemically-synthetic annexin II small interfering RNA (siRNA) duplexes (including 3 groups: blank MDA-MB-435s cells, cells transfected with negative control siRNA, and cells transfected with annexin II-siRNA). Finally, the cell proliferation, invasion, and plasmin generation were assayed, and the cellular levels of S100A10 and c-Myc were also detected. All the tests were repeated 3 times.
RESULTS: Annexin II and S100A10 were over expressed in invasive human breast cancer cell lines. The siRNA targeting annexin II of MDA-MB-435s cells did not only decrease annexin II messenger RNA and protein levels, but also down-regulated the levels of S100A10, and c-Myc. The treated cells were remarkably blocked in the G0/G1 phase, and cells in the S/G2+M phase decreased. Additionally, the treatment with siRNA resulted in reduction of plasmin generation as well as a loss of the invasive capacity of breast cancer cells.
CONCLUSION: Annexin II might be a key contributor to breast cancer proliferation and invasion.

Leclerc E, Heizmann CW, Vetter SW
RAGE and S100 protein transcription levels are highly variable in human melanoma tumors and cells.
Gen Physiol Biophys. 2009; 28 Spec No Focus:F65-75 [PubMed] Related Publications
The Receptor for Advanced Glycation Endproducts (RAGE) has been suggested to play an important role in melanoma. Animal studies with anti-RAGE antibodies have shown that RAGE blockade leads to reduced melanoma tumor growth and metastasis formation. RAGE is a multiligand receptor and among its ligands are the Ca-binding S100 proteins. Certain S100 proteins are differentially expressed in melanoma. For example, S100B is currently used as a reliable prognostic biomarker in patients with malignant melanoma. We have surveyed 40 human melanoma tumor samples for the transcription of RAGE and five of its known S100 protein ligands. Compared to normal skin tissue, we found highly significant (p < 0.0001) over-expression of S100B and underexpression of S100A2, whereas no significant difference in transcription of S100A6 and S100A10 was observed. RAGE showed slightly increased transcription in stage IV. Between individual tumor samples tremendous differences in transcription of the S100 proteins were observed, whereas RAGE expression showed relatively little variance. We also analyzed three well-characterized melanoma cell lines for S100 and RAGE expression. The S100 protein transcription profile showed clear differences between cultured melanoma cells and melanoma tumor tissue. Detailed profiling of S100 and RAGE transcription in melanoma tumors in combination with imunohisto-chemical and clinical data may lead to improved molecular diagnostic of melanoma and subsequently may facilitate improved treatment in the future.

Petersson S, Shubbar E, Enerbäck L, Enerbäck C
Expression patterns of S100 proteins in melanocytes and melanocytic lesions.
Melanoma Res. 2009; 19(4):215-25 [PubMed] Related Publications
S100 proteins are differentially expressed in tumours of epithelial origin. Little is known about their expression in melanocyte-derived tumours of neuroectodermal origin. We have analysed the expression of some S100 proteins in this line of lesions using SAGE Genie informatics, cell culture and human tumour tissue. The pattern of expression of six S100 proteins was investigated at both the mRNA and protein levels, using quantitative real-time PCR, western blotting and immunohistochemical analysis. No differential expression was observed with respect to S100A4, S100A7, S100A8, S100A9 and S100A11. In contrast, S100A10 was downregulated in three melanoma cell lines compared with normal melanocytes. Using SAGE informatics, two-dimensional displays of microarray expression data from the NCI60_Novartis cell lines displayed a positive correlation between the expression of S100A10 and the expression of the proliferation marker, Ki67. Our data suggest that S100A10, like its binding partners S100A7 and annexin A2, is an oxidant-sensitive protein. In addition, higher expression of S100A10 was detected in melanocyte cell lines with long projections compared with melanoma cell lines with small ripples. In a panel of 47 melanocyte-derived lesions comprising melanocytic naevi and melanomas, S100A10 was expressed to varying degrees in the melanocytic lesions. The antigen was primarily expressed in regions with a strong proliferating or differentiating capacity, especially in regions in or near the epidermis. We suggest that S100A10 may play a role in the regulation of the proliferation or early maturation sequence of melanocytic lesions, and that it merits further study as a potential biomarker of activity.

Inokuchi J, Narula N, Yee DS, et al.
Annexin A2 positively contributes to the malignant phenotype and secretion of IL-6 in DU145 prostate cancer cells.
Int J Cancer. 2009; 124(1):68-74 [PubMed] Related Publications
Several groups, including ours, have reported that annexin A2 (ANXA2) expression is reduced in most prostate cancer (CaP). More recently, however, we reported that ANXA2 is expressed in some high-grade tumors, but the biologic consequence of this is currently unknown. To elucidate the function of ANXA2 in CaP, we reduced its expression in DU145 cells using shRNA and tested the impact on characteristics of malignancy. Reduction of ANXA2 suppressed anchorage-dependent and -independent cell growth without affecting invasiveness. Interestingly, interleukin-6 (IL-6) secretion was reduced concomitantly with the reduction of ANXA2 but independently of S100A10. IL-6 expression was restored when wild type but not mutant ANXA2 was reexpressed in these cells. In a retrospective study of radical prostatectomy specimens from patients with nonmetastatic CaP, 100% of patients with ANXA2-positive tumors (n = 4) had a biochemical relapse while only 50% of patients with ANXA2 negative tumors (n = 20) relapsed, suggesting that ANXA2 expression in prostate tumors may be predictive of biochemical relapse. Significant cytoplasmic staining of ANXA2 was detected in 3 of 4 ANXA2-positive tumors, whereas ANXA2 is localized to the plasma membrane in benign prostatic glands. These finding, taken together, suggests a possible mechanism whereby ANXA2 expression positively contributes to an aggressive phenotype in a subset of CaP and suggest that ANXA2 has markedly different functions depending on its cellular context. Finally, this is the first description of a role for ANXA2 in IL-6 expression, and ANXA2 represents a new therapeutic target for reducing IL-6 in high-grade prostate cancer.

Dudley KJ, Revill K, Whitby P, et al.
Genome-wide analysis in a murine Dnmt1 knockdown model identifies epigenetically silenced genes in primary human pituitary tumors.
Mol Cancer Res. 2008; 6(10):1567-74 [PubMed] Related Publications
DNA methylation at promoter CpG islands (CGI) is an epigenetic modification associated with inappropriate gene silencing in multiple tumor types. In the absence of a human pituitary tumor cell line, small interfering RNA-mediated knockdown of the maintenance methyltransferase DNA methyltransferase (cytosine 5)-1 (Dnmt1) was used in the murine pituitary adenoma cell line AtT-20. Sustained knockdown induced reexpression of the fully methylated and normally imprinted gene neuronatin (Nnat) in a time-dependent manner. Combined bisulfite restriction analysis (COBRA) revealed that reexpression of Nnat was associated with partial CGI demethylation, which was also observed at the H19 differentially methylated region. Subsequent genome-wide microarray analysis identified 91 genes that were significantly differentially expressed in Dnmt1 knockdown cells (10% false discovery rate). The analysis showed that genes associated with the induction of apoptosis, signal transduction, and developmental processes were significantly overrepresented in this list (P < 0.05). Following validation by reverse transcription-PCR and detection of inappropriate CGI methylation by COBRA, four genes (ICAM1, NNAT, RUNX1, and S100A10) were analyzed in primary human pituitary tumors, each displaying significantly reduced mRNA levels relative to normal pituitary (P < 0.05). For two of these genes, NNAT and S100A10, decreased expression was associated with increased promoter CGI methylation. Induced expression of Nnat in stable transfected AtT-20 cells inhibited cell proliferation. To our knowledge, this is the first report of array-based "epigenetic unmasking" in combination with Dnmt1 knockdown and reveals the potential of this strategy toward identifying genes silenced by epigenetic mechanisms across species boundaries.

Liu J, Li X, Dong GL, et al.
In silico analysis and verification of S100 gene expression in gastric cancer.
BMC Cancer. 2008; 8:261 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The S100 protein family comprises 22 members whose protein sequences encompass at least one EF-hand Ca2+ binding motif. They were involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. However, the expression status of S100 family members in gastric cancer was not known yet.
METHODS: Combined with analysis of series analysis of gene expression, virtual Northern blot and microarray data, the expression levels of S100 family members in normal and malignant stomach tissues were systematically investigated. The expression of S100A3 was further evaluated by quantitative RT-PCR.
RESULTS: At least 5 S100 genes were found to be upregulated in gastric cancer by in silico analysis. Among them, four genes, including S100A2, S100A4, S100A7 and S100A10, were reported to overexpressed in gastric cancer previously. The expression of S100A3 in eighty patients of gastric cancer was further examined. The results showed that the mean expression levels of S100A3 in gastric cancer tissues were 2.5 times as high as in adjacent non-tumorous tissues. S100A3 expression was correlated with tumor differentiation and TNM (Tumor-Node-Metastasis) stage of gastric cancer, which was relatively highly expressed in poorly differentiated and advanced gastric cancer tissues (P < 0.05).
CONCLUSION: To our knowledge this is the first report of systematic evaluation of S100 gene expressions in gastric cancers by multiple in silico analysis. The results indicated that overexpression of S100 gene family members were characteristics of gastric cancers and S100A3 might play important roles in differentiation and progression of gastric cancer.

Rand V, Prebble E, Ridley L, et al.
Investigation of chromosome 1q reveals differential expression of members of the S100 family in clinical subgroups of intracranial paediatric ependymoma.
Br J Cancer. 2008; 99(7):1136-43 [PubMed] Free Access to Full Article Related Publications
Gain of 1q is one of the most common alterations in cancer and has been associated with adverse clinical behaviour in ependymoma. The aim of this study was to investigate this region to gain insight into the role of 1q genes in intracranial paediatric ependymoma. To address this issue we generated profiles of eleven ependymoma, including two relapse pairs and seven primary tumours, using comparative genome hybridisation and serial analysis of gene expression. Analysis of 656 SAGE tags mapping to 1q identified CHI3L1 and S100A10 as the most upregulated genes in the relapse pair with de novo 1q gain upon recurrence. Moreover, three more members of the S100 family had distinct gene expression profiles in ependymoma. Candidates (CHI3L1, S100A10, S100A4, S100A6 and S100A2) were validated using immunohistochemistry on a tissue microarray of 74 paediatric ependymoma. In necrotic cases, CHI3L1 demonstrated a distinct staining pattern in tumour cells adjacent to the areas of necrosis. S100A6 significantly correlated with supratentorial tumours (P<0.001) and S100A4 with patients under the age of 3 years at diagnosis (P=0.038). In conclusion, this study provides evidence that S100A6 and S100A4 are differentially expressed in clinically relevant subgroups, and also demonstrates a link between CHI3L1 protein expression and necrosis in intracranial paediatric ependymoma.

Anderton JA, Lindsey JC, Lusher ME, et al.
Global analysis of the medulloblastoma epigenome identifies disease-subgroup-specific inactivation of COL1A2.
Neuro Oncol. 2008; 10(6):981-94 [PubMed] Free Access to Full Article Related Publications
Candidate gene investigations have indicated a significant role for epigenetic events in the pathogenesis of medulloblastoma, the most common malignant brain tumor of childhood. To assess the medulloblastoma epigenome more comprehensively, we undertook a genomewide investigation to identify genes that display evidence of methylation-dependent regulation. Expression microarray analysis of medulloblastoma cell lines following treatment with a DNA methyltransferase inhibitor revealed deregulation of multiple transcripts (3%-6% of probes per cell line). Eighteen independent genes demonstrated >3-fold reactivation in all cell lines tested. Bisulfite sequence analysis revealed dense CpG island methylation associated with transcriptional silencing for 12 of these genes. Extension of this analysis to primary tumors and the normal cerebellum revealed three major classes of epigenetically regulated genes: (1) normally methylated genes (DAZL, ZNF157, ASN) whose methylation reflects somatic patterns observed in the cerebellum, (2) X-linked genes (MSN, POU3F4, HTR2C) that show disruption of their sex-specific methylation patterns in tumors, and (3) tumor-specific methylated genes (COL1A2, S100A10, S100A6, HTATIP2, CDH1, LXN) that display enhanced methylation levels in tumors compared with the cerebellum. Detailed analysis of COL1A2 supports a key role in medulloblastoma tumorigenesis; dense biallelic methylation associated with transcriptional silencing was observed in 46 of 60 cases (77%). Moreover, COL1A2 status distinguished infant medulloblastomas of the desmoplastic histopathological subtype, indicating that distinct molecular pathogenesis may underlie these tumors and their more favorable prognosis. These data reveal a more diverse and expansive medulloblastoma epi genome than previously understood and provide strong evidence that the methylation status of specific genes may contribute to the biological subclassification of medulloblastoma.

Hou Y, Yang L, Mou M, et al.
Annexin A2 regulates the levels of plasmin, S100A10 and Fascin in L5178Y cells.
Cancer Invest. 2008; 26(8):809-15 [PubMed] Related Publications
Annexin A2 (ANXA2) was reported as the receptor, activator, expression enhancer, or cooperator for plasmin, S100A10, and others. To delineate the effect of ANXA2 on the proteins that are probably associated with tumor development and metastasis by a credible experimental method, we generated an ANXA2 gene knockout tumor cell line, ANXA2(-/-) L5178Y, and compared the expression levels of plasmin, S100A10 and fascin in the generated cell line with in wild type of L5178Y at mRNA and protein levels. The results showed that the mRNA level of plasminogen (PLG) was not substantially changed in cultured ANXA2(-/-) cells, but the protein level of plasmin was significantly lower in the cultured ANXA2(-/-) cells than in cultured ANXA2(+/+) cells. For S100A10 and fascin, their mRNA and protein levels were significantly lower in the cultured ANXA2(-/-) cells than in cultured ANXA2(+/+) cells. Results indicate that ANXA2 introduces the generation or expression of plasmin, S100A10, and fascin in tumor cells. ANXA2 affects PLG/plasmin level by a way post transcription and may be an inducer or enhancer to fascin expression at transcription level. By the regulations, ANXA2 enhances the development, invasion, and metastasis of tumor. The detailed mechanism for the regulations above remains to be further investigated, but our results show the potential of ANXA2 as a new target molecule for the strategies of tumor biotherapy or tumor gene therapy.

Kittaka N, Takemasa I, Takeda Y, et al.
Molecular mapping of human hepatocellular carcinoma provides deeper biological insight from genomic data.
Eur J Cancer. 2008; 44(6):885-97 [PubMed] Related Publications
DNA microarray analysis of human cancer has resulted in considerable accumulation of global gene profiles. However, extraction and understanding the underlying biology of cancer progression remains a significant challenge. This study applied a novel integrative computational and analytical approach to this challenge in human hepatocellular carcinoma (HCC) with the aim of identifying potential molecular markers or novel therapeutic targets. We analysed 100 HCC tissue samples by human 30K DNA microarray. The gene expression data were uploaded into the network analysis tool, and the biological networks were displayed graphically. We identified several activated 'hotspot' regions harbouring a concentration of upregulated genes. Several 'hotspot' regions revealed integrin and Akt/NF-kappaB signalling. We identified key members linked to these signalling pathways including osteopontin (SPP1), glypican-3 (GPC3), annexin 2 (ANXA2), S100A10 and vimentin (VIM). Our integrative approach should significantly enhance the power of microarray data in identifying novel potential targets in human cancer.

Lindsey JC, Lusher ME, Anderton JA, et al.
Epigenetic deregulation of multiple S100 gene family members by differential hypomethylation and hypermethylation events in medulloblastoma.
Br J Cancer. 2007; 97(2):267-74 [PubMed] Free Access to Full Article Related Publications
Deregulated expression of genes encoding members of the S100 family of calcium-binding proteins has been associated with the malignant progression of multiple tumour types. Using a pharmacological expression reactivation approach, we screened 16 S100 genes for evidence of epigenetic regulation in medulloblastoma, the most common malignant brain tumour of childhood. Four family members (S100A2, S100A4, S100A6 and S100A10) demonstrated evidence of upregulated expression in multiple medulloblastoma cell lines, following treatment with the DNA methyltransferase inhibitor, 5'-aza-2'-deoxycytidine. Subsequent analysis revealed methylation of critical CpG sites located within these four genes in an extended cell line panel. Assessment of these genes in the non-neoplastic cerebellum (from which medulloblastomas develop) revealed strong somatic methylation affecting S100A2 and S100A4, whereas S100A6 and S100A10 were unmethylated. Assessed against these normal tissue-specific methylation states, S100A6 and S100A10 demonstrated tumour-specific hypermethylation in medulloblastoma primary tumours (5 out of 40 and 4 out of 35, respectively, both 12%) and cell lines (both 7 out of 9, 78%), which was associated with their transcriptional silencing. Moreover, S100A6 hypermethylation was significantly associated with the aggressive large cell/anaplastic morphophenotype (P=0.026). In contrast, pro-metastatic S100A4 displayed evidence of hypomethylation relative to the normal cerebellum in a significant proportion primary tumours (7 out of 41, 17%) and cell lines (3 out of 9, 33%), which was associated with its elevated expression. In summary, these data characterise complex patterns of somatic methylation affecting S100 genes in the normal cerebellum and demonstrate their disruption causing epigenetic deregulation of multiple S100 family members in medulloblastoma development. Epigenetic events affecting S100 genes have potential clinical utility and merit further investigation as molecular biomarkers for this disease.

Chari R, Lockwood WW, Coe BP, et al.
SIGMA: a system for integrative genomic microarray analysis of cancer genomes.
BMC Genomics. 2006; 7:324 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The prevalence of high resolution profiling of genomes has created a need for the integrative analysis of information generated from multiple methodologies and platforms. Although the majority of data in the public domain are gene expression profiles, and expression analysis software are available, the increase of array CGH studies has enabled integration of high throughput genomic and gene expression datasets. However, tools for direct mining and analysis of array CGH data are limited. Hence, there is a great need for analytical and display software tailored to cross platform integrative analysis of cancer genomes.
RESULTS: We have created a user-friendly java application to facilitate sophisticated visualization and analysis such as cross-tumor and cross-platform comparisons. To demonstrate the utility of this software, we assembled array CGH data representing Affymetrix SNP chip, Stanford cDNA arrays and whole genome tiling path array platforms for cross comparison. This cancer genome database contains 267 profiles from commonly used cancer cell lines representing 14 different tissue types.
CONCLUSION: In this study we have developed an application for the visualization and analysis of data from high resolution array CGH platforms that can be adapted for analysis of multiple types of high throughput genomic datasets. Furthermore, we invite researchers using array CGH technology to deposit both their raw and processed data, as this will be a continually expanding database of cancer genomes. This publicly available resource, the System for Integrative Genomic Microarray Analysis (SIGMA) of cancer genomes, can be accessed at http://sigma.bccrc.ca.

Domoto T, Miyama Y, Suzuki H, et al.
Evaluation of S100A10, annexin II and B-FABP expression as markers for renal cell carcinoma.
Cancer Sci. 2007; 98(1):77-82 [PubMed] Related Publications
This study aimed to analyze expression of S100A10, annexin II and B-FABP genes in renal cell carcinoma (RCC) and their potential value as tumor markers. Furthermore, any correlation between the gene expression and prognostic indicators of RCC was analyzed. Expression of each gene was estimated by RT-PCR in the non-neoplastic (normal) and tumorous parts of resected kidney samples. Also, each antigen was immunostained in RCC and normal kidney tissues. Expression of the S100A10 gene averaged 2.5-fold higher in the tumor than that in the normal tissues (n = 47), after standardization against that of beta-actin. However, expression of annexin II, a natural ligand of S100A10, was only 1.64-fold higher. In the tissue sections of RCC, S100A10 and annexin II were immunostained in membranes. In the normal renal epithelia, however, both antigens were stained in the Bowman's capsule and the tubules from Henle's loop through the collecting duct system, but not in the proximal tubules, from where most RCC are derived. In contrast, expression of the B-FABP gene was 20-fold higher in the tumor. No B-FABP was immunohistochemically detected in normal kidney sections, but it was stained in the cytoplasm of RCC tissue sections. S100A10 and B-FABP genes were overexpressed regardless of nuclear grade and stage of RCC. Immunopositivity in RCC tissues (n = 13) was 100% for S100A10 and annexin II, and 70% for B-FABP; however, no clear relationship was observed in either antigen with nuclear grade and stage. It was found that all three performed well as RCC markers. B-FABP was most specific to RCC, as it was expressed little in normal kidney tissues.

Tsai CJ, Herrera-Goepfert R, Tibshirani RJ, et al.
Changes of gene expression in gastric preneoplasia following Helicobacter pylori eradication therapy.
Cancer Epidemiol Biomarkers Prev. 2006; 15(2):272-80 [PubMed] Related Publications
Helicobacter pylori causes gastric preneoplasia and neoplasia. Eradicating H. pylori can result in partial regression of preneoplastic lesions; however, the molecular underpinning of this change is unknown. To identify molecular changes in the gastric mucosa following H. pylori eradication, we used cDNA microarrays (with each array containing approximately 30,300 genes) to analyze 54 gastric biopsies from a randomized, placebo-controlled trial of H. pylori therapy. The 54 biopsies were obtained from 27 subjects (13 from the treatment and 14 from the placebo group) with chronic gastritis, atrophy, and/or intestinal metaplasia. Each subject contributed one biopsy before and another biopsy 1 year after the intervention. Significant analysis of microarrays (SAM) was used to compare the gene expression profiles of pre-intervention and post-intervention biopsies. In the treatment group, SAM identified 30 genes whose expression changed significantly from baseline to 1 year after treatment (0 up-regulated and 30 down-regulated). In the placebo group, the expression of 55 genes differed significantly over the 1-year period (32 up-regulated and 23 down-regulated). Five genes involved in cell-cell adhesion and lining (TACSTD1 and MUC13), cell cycle differentiation (S100A10), and lipid metabolism and transport (FABP1 and MTP) were down-regulated over time in the treatment group but up-regulated in the placebo group. Immunohistochemistry for one of these differentially expressed genes (FABP1) confirmed the changes in gene expression observed by microarray. In conclusion, H. pylori eradication may stop or reverse ongoing molecular processes in the stomach. Further studies are needed to evaluate the use of these genes as markers for gastric cancer risk.

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