Gene Summary

Gene:SSTR1; somatostatin receptor 1
Aliases: SS1R, SS1-R, SRIF-2, SS-1-R
Summary:Somatostatins are peptide hormones that regulate diverse cellular functions such as neurotransmission, cell proliferation, and endocrine signaling as well as inhibiting the release of many hormones and other secretory proteins. Somatostatin has two active forms of 14 and 28 amino acids. The biological effects of somatostatins are mediated by a family of G-protein coupled somatostatin receptors that are expressed in a tissue-specific manner. The protein encoded by this gene is a member of the superfamily of somatostatin receptors having seven transmembrane segments. Somatostatin receptors form homodimers and heterodimers with other members of the superfamily as well as with other G-protein coupled receptors and receptor tyrosine kinases. This somatostatin receptor has greater affinity for somatostatin-14 than -28. [provided by RefSeq, Jul 2012]
Databases:OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene
Protein:somatostatin receptor type 1
Source:NCBIAccessed: 17 March, 2015


What does this gene/protein do?
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Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

Research Indicators

Publications Per Year (1990-2015)
Graph generated 17 March 2015 using data from PubMed using criteria.

Literature Analysis

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Tag cloud generated 17 March, 2015 using data from PubMed, MeSH and CancerIndex

Latest Publications: SSTR1 (cancer-related)

Wang S, Bao Z, Liang QM, et al.
Octreotide stimulates somatostatin receptor-induced apoptosis of SW480 colon cancer cells by activation of glycogen synthase kinase-3β, A Wnt/β-catenin pathway modulator.
Hepatogastroenterology. 2013; 60(127):1639-46 [PubMed] Related Publications
BACKGROUND/AIMS: Peptide hormone somatostatin and its receptors (SSTRs) have a wide range of physiological functions and play a role in the treatment of numerous human diseases, including colorectal cancer. Octreotide, a somatostatin-analog peptide, inhibits growth of colonic cancer SW480 cells through Wnt/β-catenin pathway modulation. However, the specific octreotide-stimulating SSTR subtypes and the signal-transduction mechanism responsible for the negative regulation of Wnt/β-catenin pathway by octreotide have not been fully elucidated.
METHODOLOGY: Octreotide-induced apoptosis in SW480 colon cancer cells mediated by SSTR2,SSTR5-dependent regulation of the Wnt/β-catenin pathway components GSK-3β and β-catenin was investigated. Cell apoptosis of SW480 cells was measured by apoptosis-DNA ladder assay. SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 mRNA expression levels were confirmed by RT-PCR; β-catenin, TCF-4, cyclin D1, c-Myc, and GSK-3β protein levels were examined by Western blot. The distribution of β-catenin in the cell was analyzed with immunocytochemistry.
RESULTS: Octreotide treatment increased SSTR2,SSTR5-induced apoptosis of SW480 colon cancer cells, promoted the plasma membrane accumulation of β-catenin, inactivated T-cell factor-dependent transcription, and downregulated Wnt target genes cyclin D1 and c-Myc. Further, octreotide treatment mediated the activation of GSK-3.
CONCLUSIONS: These preliminary findings showed the negative regulation of the Wnt/β-catenin pathway by peptide hormone G protein-coupled receptors SSTRs.

Ruscica M, Magni P, Steffani L, et al.
Characterization and sub-cellular localization of SS1R, SS2R, and SS5R in human late-stage prostate cancer cells: effect of mono- and bi-specific somatostatin analogs on cell growth.
Mol Cell Endocrinol. 2014; 382(2):860-70 [PubMed] Related Publications
Somatostatin (SST) and SST receptors (SS1R, SS2R, SS3R, SS4R and SS5R) appear to play a significant role in the progression of human prostate cancer (PCa), which is associated with heterogeneity of SSRs expression and specific cell localization as we already demonstrated in the LNCaP cell line, an in vitro model of human androgen-dependent PCa. In this study, PC-3 and DU-145 human castration-resistant PCa cells were found to express all SSRs, while LNCaP expressed all but SS4R. A 48-h treatment with BIM-23244 (SS2R/SS5R) or BIM-23926 (SS1R) SST analogs was more effective in inhibiting cell proliferation, compared to BIM-23120 (SS2R), BIM-23206 (SS5R) and BIM-23704 (SS1R/SS2R). BIM-23926 (SS1R) treatment increased the amount of p21 and decreased phosphorylated (p) ERK1/2. BIM-23244 (SS2R/SS5R) led to p21 increment only in PC-3 cells, and to pERK1/2 reduction in both cell lines. SS1R/SS2R and SS2R/SS5R receptor dimers were natively present on cell membrane and their amount was increased by BIM-23704 (SS1R/SS2R) or BIM-23244 (SS2R/SS5R) treatment, respectively. SS1R, SS2R and SS5R were differently distributed among nuclear, lysosomal and microsomal compartment, according to their different recycling dynamics. These results show that, in PC-3, DU-145 and LNCaP cells, activation of SS1R and SS2R/SS5R leads to relevant antiproliferative effects.

Vieria Neto L, Wildemberg LE, Colli LM, et al.
ZAC1 and SSTR2 are downregulated in non-functioning pituitary adenomas but not in somatotropinomas.
PLoS One. 2013; 8(10):e77406 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: There are few data regarding ZAC1 expression in clinically non-functioning pituitary adenomas (NFPA). Because somatotropinomas and NFPA behave differently with respect to tumor shrinkage during somatostatin analogs (SA) therapy, we sought to compare the ZAC1 and somatostatin receptor (sstr) types 1, 2, 3 and 5 mRNA expression in these two pituitary adenoma subtypes and in normal human pituitaries.
METHODS: ZAC1 and SSTR mRNA expression levels were evaluated using real-time RT-PCR (TaqMan) in 20 NFPA and compared with the expression levels in 23 somatotropinomas and five normal pituitaries. The NFPA invasiveness was evaluated using magnetic resonance imaging with Hardy's modified criteria. Ki-67 and p53 were evaluated using immunohistochemistry.
RESULTS: A total of 20 patients with NFPA [6 males, median age 56 years (range: 30-78)], 23 with acromegaly [12 males, median age 43 years (range: 24-57)] and five normal pituitaries [4 males, median age 48 years (range: 36-54)] were included. Four of the patients (20%) had Hardy's grade 2 tumors; all of the others had Hardy's grade 3 tumors. The Ki-67 median expression was 2.35 (range: 0.2-9.23), and only four of the tumors (20%) were positive for p53. The ZAC1 mRNA expression was significantly lower in NFPA than in somatotropinomas and in normal pituitaries (p<0.001 for both), as well as the SSTR2 (p=0.001 and 0.01, respectively). The SSTR3 expression was higher in the NFPA than in the somatotropinomas and in the normal pituitaries (p=0.03 and 0.02, respectively). No correlation was found between the ZAC1 mRNA expression and the tumor invasiveness, Ki-67 and p53.
CONCLUSION: ZAC1 and SSTR2 are underexpressed and SSTR3 is overexpressed in NFPA compared to those in somatotropinomas and in normal pituitaries, which might explain the lack of tumor shrinkage that is observed in response to commercially available SA therapy in patients with NFPA.

Mayr B, Buslei R, Theodoropoulou M, et al.
Molecular and functional properties of densely and sparsely granulated GH-producing pituitary adenomas.
Eur J Endocrinol. 2013; 169(4):391-400 [PubMed] Related Publications
OBJECTIVE: GH-producing pituitary adenomas display two distinct morphological patterns of cytoplasmic GH-containing secretory granules, namely the densely and sparsely granulated somatotroph adenoma subtype. It is unknown whether these morphological variants reflect distinct pathophysiological entities at the molecular level.
METHODS: In 28 GH-producing adenoma tissues from a consecutive set of patients undergoing pituitary surgery for acromegaly, we studied the GH granulation pattern, the expression of somatostatin receptor subtypes (SSTR) as well as the calcium, cAMP and ZAC1 pathways in primary adenoma cell cultures.
RESULTS: The expression of GSP oncogene was similar between densely and sparsely granulated somatotroph adenoma cells. There were no differences in the calcium, cAMP and ZAC1 pathways as well as in their regulation by SSTR agonists. SSTR2 was exclusively expressed in densely but not in sparsely granulated tumours (membrane expression 86 vs 0%; cytoplasmic expression 67 vs 0%). By contrast, expression of SSTR5 was only found in sparsely but not in densely granulated somatotroph adenomas (membrane expression 29 vs 0%; cytoplasmic expression 57 vs 0%).
CONCLUSIONS: Our results indicate that different granulation patterns in GH-producing adenomas do not reflect differences in pathways and factors pivotal for somatotroph differentiation and function. In vitro, the vast majority of both densely and sparsely granulated tumour cells were responsive to SSTR activation at the molecular level. Sparsely granulated adenomas lacking SSTR2, but expressing SSTR5, might be responsive to novel SSTR agonists with increased affinity to SSTR5.

Zhao J, Liang Q, Cheung KF, et al.
Somatostatin receptor 1, a novel EBV-associated CpG hypermethylated gene, contributes to the pathogenesis of EBV-associated gastric cancer.
Br J Cancer. 2013; 108(12):2557-64 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Somatostatin receptor 1 (SSTR1) was preferentially methylated in Epstein-Barr virus (EBV)-positive gastric cancer using promoter methylation array. We aimed to analyse the epigenetic alteration and biological function of SSTR1 in EBV-associated gastric cancer (EBVaGC).
METHODS: Promoter methylation was examined by combined bisulphite restriction analysis (COBRA) and pyrosequencing. The biological functions of SSTR1 were evaluated by loss- and gain-of-function assays.
RESULTS: Promoter hypermethylation of SSTR1 was detected in EBV-positive gastric cancer cell lines (AGS-EBV) with SSTR1 transcriptional silence, but not in EBV-negative gastric cancer cell lines with SSTR1 expression. Expression level of SSTR1 was restored in AGS-EBV by exposure to demethylating agent. Moreover, methylation level of SSTR1 was significantly higher in EBV-positive primary gastric cancers compared with EBV-negative gastric cancers (P=0.004). Knock-down of SSTR1 in gastric cancer cell lines (AGS and BGC823) increased cell proliferation and colony formation ability, and promoted G1 to S-phase transition, enhanced cell migration and invasive ability. In contrast, ectopic expression of SSTR1 in gastric cancer cell lines (MKN28 and MGC803) significantly suppressed cell growth in culture conditions and reduced tumour size in nude mice. The tumour suppressive effect of SSTR1 was associated with upregulation of cyclin-dependent kinase inhibitors (p16, p15, p27 and p21); downregulation of oncogenes (MYC and MDM2), key cell proliferation and pro-survival regulators (PI3KR1, AKT, BCL-XL and MET); and inhibition of the migration/invasion-related genes (integrins, MMP1 (matrix metallopeptidase 1), PLAUR (plasminogen activator urokinase receptor) and IL8 (interleukin 8)).
CONCLUSION: Somatostatin receptor 1 is a novel methylated gene driven by EBV infection in gastric cancer cells and acts as a potential tumour suppressor.

Niesen CE, Xu J, Fan X, et al.
Transcriptomic profiling of human peritumoral neocortex tissues revealed genes possibly involved in tumor-induced epilepsy.
PLoS One. 2013; 8(2):e56077 [PubMed] Free Access to Full Article Related Publications
The molecular mechanism underlying tumor-induced epileptogenesis is poorly understood. Alterations in the peritumoral microenvironment are believed to play a significant role in inducing epileptogenesis. We hypothesize that the change of gene expression in brain peritumoral tissues may contribute to the increased neuronal excitability and epileptogenesis. To identify the genes possibly involved in tumor-induced epilepsy, a genome-wide gene expression profiling was conducted using Affymetrix HG U133 plus 2.0 arrays and RNAs derived from formalin-fixed paraffin embedded (FFPE) peritumoral cortex tissue slides from 5-seizure vs. 5-non-seizure low grade brain tumor patients. We identified many differentially expressed genes (DEGs). Seven dysregulated genes (i.e., C1QB, CALCRL, CCR1, KAL1, SLC1A2, SSTR1 and TYRO3) were validated by qRT-PCR, which showed a high concordance. Principal Component Analysis (PCA) showed that epilepsy subjects were clustered together tightly (except one sample) and were clearly separated from the non-epilepsy subjects. Molecular functional categorization showed that significant portions of the DEGs functioned as receptor activity, molecular binding including enzyme binding and transcription factor binding. Pathway analysis showed these DEGs were mainly enriched in focal adhesion, ECM-receptor interaction, and cell adhesion molecules pathways. In conclusion, our study showed that dysregulation of gene expression in the peritumoral tissues may be one of the major mechanisms of brain tumor induced-epilepsy. However, due to the small sample size of the present study, further validation study is needed. A deeper characterization on the dysregulated genes involved in brain tumor-induced epilepsy may shed some light on the management of epilepsy due to brain tumors.

Arne G, Nilsson B, Dalmo J, et al.
Gastrointestinal stromal tumors (GISTs) express somatostatin receptors and bind radiolabeled somatostatin analogs.
Acta Oncol. 2013; 52(4):783-92 [PubMed] Related Publications
BACKGROUND: Gastrointestinal stromal tumors (GISTs) can be effectively treated with tyrosine kinase inhibitors (TKIs). However, some patients with GIST develop drug resistance, and alternative treatment strategies are therefore needed. The aim of this study was to analyze the expression of somatostatin receptors (SSTR) in GIST as a target for peptide receptor-mediated radiotherapy (PRRT).
MATERIAL AND METHODS: Expression profiling of SSTR1-5 was performed on biopsies from 34 GISTs (16 gastric tumors, 15 small intestinal tumors, and three rectal tumors). SSTR scintigraphy ((111)In-octreotide) and measurement of (111)In activity in tumor specimens was performed in seven patients. Uptake and internalization of (177)Lu- octreotate was studied in primary cell cultures from two patients.
RESULTS: Quantitative PCR analysis showed expression of SSTR1 and SSTR2 in the majority of tumors, while SSTR3-5 were expressed at low levels. Immunohistochemical analysis confirmed the presence of SSTR1 and SSTR2 proteins in all GISTs, and SSTR3-5 in a subset of tumors. Diagnostic imaging by SSTR scintigraphy, using (111)In-octreotide, demonstrated tumor uptake of (111)In in three of six GIST patients. Measurement of (111)In activity in excised tumor specimens from five patients gave tumor-to-blood (T/B) activity ratios of between eight and 96. Tumor cells in primary culture (gastric and small intestinal GIST) specifically bound and internalized (177)Lu when incubated with the therapeutic compound (177)Lu-octreotate for 4-48 hours (p < 0.05).
CONCLUSION: Peptide receptor-mediated radiotherapy via SSTR may provide a novel treatment strategy in carefully selected GIST patients with TKI-resistant tumors.

Zhao J, Liang Q, Cheung KF, et al.
Genome-wide identification of Epstein-Barr virus-driven promoter methylation profiles of human genes in gastric cancer cells.
Cancer. 2013; 119(2):304-12 [PubMed] Related Publications
BACKGROUND: Aberrant methylation of tumor-related genes has been reported in Epstein-Barr virus (EBV)-associated gastric cancers. This study sought to profile EBV-driven hypermethylation in EBV-infected cells.
METHODS: The EBV-positive AGS gastric cancer cell line (AGS-EBV) and EBV-negative AGS cells were used in this study. DNA methyltransferase-3b (DNMT3b) activity was assessed by EpiQuick activity assay, and genome-wide DNA methylation profiles were assessed by methyl-DNA immunoprecipitation microarray assay.
RESULTS: EBV infection was confirmed in AGS-EBV cells by EBV-encoded RNA in situ hybridization. Expression and activity of DNA methyltransferase-3b (DNMT3b) was significantly increased in AGS-EBV compared to AGS. Ectopic expression of LMP2A (latent membrane protein 2A) in AGS increased activity of DNMT3b. A total of 1065 genes were differentially methylated by EBV infection (fold-changes ≥ 2, P < .05) in AGS-EBV compared to AGS cells. The majority of the differentially methylated genes (83.2%, 886 of 1065 genes) had cytosine-guanine dinucleotide (CpG) hypermethylation in AGS-EBV (fold-changes 2.43∼65.2) versus that found in AGS cells. Gene ontology analysis revealed that hypermethylated genes were enriched in the important cancer pathways (≥ 10 genes each, P ≤ .05) including mitogen-activated protein kinase signaling, cell adhesion molecules, wnt signaling pathway, and so forth. Six novel hypermethylated candidates (IL15RA, REC8, SSTR1, EPHB6, MDGA2, and SCARF2) were further validated. Higher levels of DNA methylation were confirmed for all these genes in AGS-EBV cells by bisulfite genomic sequencing. Furthermore, these candidates were silenced or down-regulated in AGS-EBV cells, but can be restored by demethylation treatment.
CONCLUSIONS: EBV infection in AGS cells induced aberrant CpG hypermethylation of 886 genes involving in important cancer-related pathways. Induction of promoter methylation by EBV is regulated by up-regulation of DNMT3b through LMP2A.

Franko-Tobin LG, Mackey LV, Huang W, et al.
Notch1-mediated tumor suppression in cervical cancer with the involvement of SST signaling and its application in enhanced SSTR-targeted therapeutics.
Oncologist. 2012; 17(2):220-32 [PubMed] Free Access to Full Article Related Publications
The role of Notch signaling in cervical cancer is seemingly controversial. To confirm the function of Notch signaling in this type of cancer, we established a stable Notch1-activated cervical cancer HeLa cell line. We found that Notch1 activation resulted in apoptosis, cell cycle arrest, and tumor suppression. At the molecular level, we found that a variety of genes associated with cyclic AMP, G protein-coupled receptor, and cancer signaling pathways contributed to Notch1-mediated tumor suppression. We observed that the expression of somatostatin (SST) was dramatically induced by Notch1 signaling activation, which was accompanied by enhanced expression of the cognate SST receptor subtype 1 (SSTR1) and SSTR2. Certain genes, such as tumor protein 63 (TP63, p63), were upregulated, whereas others, such as B-cell lymphoma 2 (BCL-2), Myc, Akt, and STAT3, were downregulated. Subsequently, knockdown of Notch1-induced SST reversed Notch1-induced decrease of BCL-2 and increase of p63, indicating that Notch1-induced tumor suppression may be partly through upregulating SST signaling. Our findings support a possible crosstalk between Notch signaling and SST signaling. Moreover, Notch-induced SSTR activation could enhance SSTR-targeted cancer chemotherapy. Valproic acid (VPA), a histone deacetylase inhibitor, suppressed cell growth and upregulated the expression of Notch1 and SSTR2. A combination therapy with VPA and the SSTR2-targeting cytotoxic conjugate CPT-SST strongly led to greater suppression, as compared to each alone. Our findings thus provide us with a promising clinical opportunity for enhanced cancer therapy using combinations of Notch1-activating agents and SSTR2-targeting agents.

Dalezis P, Geromichalos GD, Trafalis DT, et al.
Dexamethasone plus octreotide regimen increases anticancer effects of docetaxel on TRAMP-C1 prostate cancer model.
In Vivo. 2012 Jan-Feb; 26(1):75-86 [PubMed] Related Publications
AIM: The aim of this study was to evaluate whether the neoadjuvant use of the dexamethasone (DEX) plus octreotide (OCT) regimen can improve the direct anticancer effects of docetaxel (DOC) in the TRAMP-C1 prostate cancer model.
MATERIALS AND METHODS: TRAMP-C1 cells were first characterized for the expression of SSTR1-5 and then were inoculated onto the femur of C57Bl mice. Investigation protocols employed TRAMP-C1 cell proliferation and invasion assays, analysis of radiographic images of the bone lesions and overall survival of the diseased animals.
RESULTS: The triple combination treatment scheme showed significant anticancer effects, in both proliferation and invasion assays, compared to any single agent treatment scheme. DOC treatment following the neoadjuvant administration of DEX plus OCT regimen improved significantly the anticancer effects both on the grading of the bone lesions and on the overall survival of the diseased animals.
CONCLUSION: Our data suggest that the neoadjuvant administration of DEX plus OCT regimen can improve the anticancer effects of DOC on the TRAMP-C1 model.

Li H, Bitler BG, Vathipadiekal V, et al.
ALDH1A1 is a novel EZH2 target gene in epithelial ovarian cancer identified by genome-wide approaches.
Cancer Prev Res (Phila). 2012; 5(3):484-91 [PubMed] Free Access to Full Article Related Publications
Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy in the United States. EZH2 silences gene expression through trimethylating lysine 27 on histone H3 (H3K27Me3). EZH2 is often overexpressed in EOC and has been suggested as a target for EOC intervention. However, EZH2 target genes in EOC remain poorly understood. Here, we mapped the genomic loci occupied by EZH2/H3K27Me3 using chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) and globally profiled gene expression in EZH2-knockdown EOC cells. Cross-examination of gene expression and ChIP-seq revealed a list of 60 EZH2 direct target genes whose expression was upregulated more than 1.5-fold upon EZH2 knockdown. For three selected genes (ALDH1A1, SSTR1, and DACT3), we validated their upregulation upon EZH2 knockdown and confirmed the binding of EZH2/H3K27Me3 to their genomic loci. Furthermore, the presence of H3K27Me3 at the genomic loci of these EZH2 target genes was dependent upon EZH2. Interestingly, expression of ALDH1A1, a putative marker for EOC stem cells, was significantly downregulated in high-grade serous EOC (n = 53) compared with ovarian surface epithelial cells (n = 10, P < 0.001). Notably, expression of ALDH1A1 negatively correlated with expression of EZH2 (n = 63, Spearman r = -0.41, P < 0.001). Thus, we identified a list of 60 EZH2 target genes and established that ALDH1A1 is a novel EZH2 target gene in EOC cells. Our results suggest a role for EZH2 in regulating EOC stem cell equilibrium via regulation of ALDH1A1 expression.

Kaemmerer D, Peter L, Lupp A, et al.
Molecular imaging with ⁶⁸Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours.
Eur J Nucl Med Mol Imaging. 2011; 38(9):1659-68 [PubMed] Related Publications
PURPOSE: Somatostatin receptors (SSTR) are known for an overexpression in gastroenteropancreatic neuroendocrine tumours (GEP-NET). The aim of the present study was to find out if the receptor density predicted by the semi-quantitative parameters generated from the static positron emission tomography (PET/CT) correlated with the in vitro immunohistochemistry using a novel rabbit monoclonal anti-SSTR2A antibody (clone UMB-1) for specific SSTR2A immunohistochemistry and polyclonal antibodies for SSTR1 and 3-5.
METHODS: Overall 14 surgical specimens generated from 34 histologically documented GEP-NET patients were correlated with the preoperative (68)Ga-DOTA-NOC PET/CT. Quantitative assessment of the receptor density was done using the immunoreactive score (IRS) of Remmele and Stegner; the additional 4-point IRS classification for immunohistochemistry and standardized uptake values (SUV(max) and SUV(mean)) were used for PET/CT.
RESULTS: The IRS for SSTR2A and SSTR5 correlated highly significant with the SUV(max) on the PET/CT (p < 0.001; p < 0.05) and the IRS for SSTR2A with the SUV(mean) (p < 0.013). The level of SSTR2A score correlated significantly with chromogranin A staining and indirectly to the tumour grading.
CONCLUSION: The highly significant correlation between SSTR2A and SSTR5 and the SUV(max) on the (68)Ga-DOTA-NOC PET/CT scans is concordant with the affinity profile of (68)Ga-DOTA-NOC to the SSTR subtypes and demonstrates the excellent qualification of somatostatin analogues in the diagnostics of NET. This study correlating somatostatin receptor imaging using (68)Ga-DOTA-NOC PET/CT with immunohistochemically analysed SSTR also underlines the approval of therapy using somatostatin analogues, follow-up imaging as well as radionuclide therapy.

Muscarella LA, D'Alessandro V, la Torre A, et al.
Gene expression of somatostatin receptor subtypes SSTR2a, SSTR3 and SSTR5 in peripheral blood of neuroendocrine lung cancer affected patients.
Cell Oncol (Dordr). 2011; 34(5):435-41 [PubMed] Related Publications
BACKGROUND: Somatostatin (SS) acts as a universal endocrine off-switch, and also inhibits the growth of neuroendocrine tumours through its specific receptors (SSTRs). Somatostatin receptors are G-protein-coupled receptors, which are encoded by five separate genes (SSTR1-5). Short peptide analogues demonstrate specific binding only for the subgroup consisting of SSTR2a, SSTR3 and SSTR5. Moreover, previous studies reported that expression of mRNA for SSTR2a correlated with therapeutic outcome in patients with carcinoid tumours treated with somatostatin analogs.
PURPOSE: To develop and apply a Real Time Quantitative PCR technique (RT-qPCR) to compare and contrast the mRNA levels of SSTR2a, SSTR3 and SSTR5 in Neuroendocrine Lung Cancer affected patients.
METHODS: Peripheral blood samples from 21 neuroendocrine lung cancer affected patients (14 SCLC, 6 LC and 1 LCNEC) subjected to scintigraphy with (111)In-DTPA-D-Phe(1)-octreotide (OctreoScan) and 24 healthy blood donors were investigated by RT-qPCR. mRNA levels for SSTR2a, SSTR3 and SSTR5 were measured in peripheral blood samples with a relative quantification method using plasmid dilutions as calibration curves and GAPDH as reference gene.
RESULTS: A statistically significant increase in target genes/GAPDH copy number ratio was found for SSTR2a (median 38; IQR 22-141) and SSTR5 (median 51; IQR 19-499) in neuroendocrine lung cancer affected patients as compared with samples from healthy blood donors (P ≤ 0.0003 and P ≤ 0.0005). Since low levels of expression were detected in the control group for all three genes, optimal cut-off values were assessed using ROC curve analyses and were equal to 9.05 for SSTR2a and 16.97 for SSTR5. These cut off values resulted in a sensitivity of 86% (95%IC 65-95) for both markers and a specificity of 83% (95%IC 64-93%) and 79% (95%IC 60-91%) for SSTR2a and SSTR5 respectively. Comparison between OctreoScan results and RT-qPCR analysis demonstrated agreement in 76% of the cases.
CONCLUSIONS: Our results suggest that SSTR2a and SSTR5 mRNAs are detectable in peripheral blood of neuroendocrine lung cancer affected patients using real-time quantitative PCR, with a good agreement with OctreoScan. The high sensitivity of this non-invasive molecular technique suggests that this method could represent a useful tool in the clinical management of neuroendocrine lung cancers.

Turrell SJ, Whitehouse A
Mutation of herpesvirus Saimiri ORF51 glycoprotein specifically targets infectivity to hepatocellular carcinoma cell lines.
J Biomed Biotechnol. 2011; 2011:785158 [PubMed] Free Access to Full Article Related Publications
Herpesvirus saimiri (HVS) is a gamma herpesvirus with several properties that make it an amenable gene therapy vector; namely its large packaging capacity, its ability to persist as a nonintegrated episome, and its ability to infect numerous human cell types. We used RecA-mediated recombination to develop an HVS vector with a mutated virion protein. The heparan sulphate-binding region of HVS ORF51 was substituted for a peptide sequence which interacts with somatostatin receptors (SSTRs), overexpressed on hepatocellular carcinoma (HCC) cells. HVS mORF51 showed reduced infectivity in non-HCC human cell lines compared to wild-type virus. Strikingly, HVS mORF51 retained its ability to infect HCC cell lines efficiently. However, neutralisation assays suggest that HVS mORF51 has no enhanced binding to SSTRs. Therefore, mutation of the ORF51 glycoprotein has specifically targeted HVS to HCC cell lines by reducing the infectivity of other cell types; however, the mechanism for this targeting is unknown.

Taboada GF, Neto LV, Luque RM, et al.
Impact of gsp oncogene on the mRNA content for somatostatin and dopamine receptors in human somatotropinomas.
Neuroendocrinology. 2011; 93(1):40-7 [PubMed] Related Publications
INTRODUCTION: It has been reported in some series that gsp+ somatotropinomas are more sensitive to somatostatin analogues (SA) and dopamine's actions which may be related to their somatostatin receptor (SSTR) and dopamine receptor (DR) profile. No previous studies have been undertaken to evaluate the SSTR and DR profile related with the gsp status in somatotropinomas.
OBJECTIVES: To determine if (1) gsp status is correlated with response to octreotide LAR (LAR) and tumor expression patterns of SSTR1-5 and DR1-5 and (2) cAMP level can directly modulate SSTR and DR mRNA levels.
METHODS: Response to SA was evaluated by GH and IGF-I percent reduction after 3 and 6 months of treatment with LAR. Conventional PCR and sequencing were used to identify gsp+ tumors. Quantitative real-time PCR was used to determine SSTR and DR tumor expression. Primary pituitary cell cultures of primates were used to study whether SSTR and DR expression is regulated by forskolin.
RESULTS: The response to LAR did not significantly differ between patients with gsp+ and gsp- tumors; however, gsp+ tumors expressed higher levels of SSTR1, SSTR2, DR2 and a lower level of SSTR3. Forskolin increased SSTR1, SSTR2, DR1 and DR2 expression in cell cultures.
CONCLUSION: Elevated SSTR1, SSTR2, and DR2 tumor expression may help improve responsiveness to SA and DA therapy; however, this study may not have been appropriately powered to observe significant effects in the clinical response. Elevated cAMP levels could be directly responsible for the upregulation in SSTR1, SSTR2 and DR2 mRNA levels observed in gsp+ patients.

Risk MC, Knudsen BS, Coleman I, et al.
Differential gene expression in benign prostate epithelium of men with and without prostate cancer: evidence for a prostate cancer field effect.
Clin Cancer Res. 2010; 16(22):5414-23 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Several malignancies are known to exhibit a "field effect," whereby regions beyond tumor boundaries harbor histologic or molecular changes that are associated with cancer. We sought to determine if histologically benign prostate epithelium collected from men with prostate cancer exhibits features indicative of premalignancy or field effect.
EXPERIMENTAL DESIGN: Prostate needle biopsies from 15 men with high-grade (Gleason 8-10) prostate cancer and 15 age- and body mass index-matched controls were identified from a biospecimen repository. Benign epithelia from each patient were isolated by laser capture microdissection. RNA was isolated, amplified, and used for microarray hybridization. Quantitative PCR was used to determine the expression of specific genes of interest. Alterations in protein expression were analyzed through immunohistochemistry.
RESULTS: Overall patterns of gene expression in microdissected benign prostate-associated benign epithelium (BABE) and cancer-associated benign epithelium (CABE) were similar. Two genes previously associated with prostate cancer, PSMA and SSTR1, were significantly upregulated in the CABE group (false discovery rate <1%). Expression of other prostate cancer-associated genes, including ERG, HOXC4, HOXC5, and MME, were also increased in CABE by quantitative reverse transcription-PCR, although other genes commonly altered in prostate cancer were not different between the BABE and CABE samples. The expression of MME and PSMA proteins on immunohistochemistry coincided with their mRNA alterations.
CONCLUSION: Gene expression profiles between benign epithelia of patients with and without prostate cancer are very similar. However, these tissues exhibit differences in the expression levels of several genes previously associated with prostate cancer development or progression. These differences may comprise a field effect and represent early events in carcinogenesis.

Nakayama Y, Wada R, Yajima N, et al.
Profiling of somatostatin receptor subtype expression by quantitative PCR and correlation with clinicopathological features in pancreatic endocrine tumors.
Pancreas. 2010; 39(8):1147-54 [PubMed] Related Publications
OBJECTIVES: Pancreatic endocrine tumor (PET) presents variable clinical features. Five subtypes of somatostatin receptor (SSTR) are involved in hormone secretion and cell proliferation. In this paper, we explore the correlation between the SSTR subtype messenger RNA (mRNA) expression and clinicopathological features of PET.
METHODS: Twenty-one cases of PET and 5 cases of pancreatic adenocarcinomas (AC) were studied. Using total RNA extracted from paraffin sections and fresh tissues, SSTR subtype mRNA was quantified by real-time polymerase chain reaction. The hormones and MIB1 index were examined using immunohistochemical techniques.
RESULTS: The mRNA levels of SSTR1, SSTR2, SSTR3, and SSTR5 were high in PET compared with AC, whereas the expression of SSTR4 was low in PET and AC. Levels of each subtype did not vary with histological grades. Somatostatin receptor 2 levels in functioning tumors were slightly low compared with nonfunctioning tumors. Four distinct groups of PET were identified by hierarchical cluster analysis, and two of these groups showed reduced SSTR5 with elevation of MIB1 index.
CONCLUSIONS: The study showed a heterogeneous expression profile of SSTR subtype mRNA and the association of reduction in SSTR5 with high proliferative activity. Such profiling of SSTR subtypes may provide useful information on tumor biology and treatment of PET.

Ishii A, Imanishi Y, Kobayashi K, et al.
The levels of somatostatin receptors in causative tumors of oncogenic osteomalacia are insufficient for their agonist to normalize serum phosphate levels.
Calcif Tissue Int. 2010; 86(6):455-62 [PubMed] Related Publications
Oncogenic osteomalacia (OOM) is a rare disease characterized by renal phosphate wasting and osteomalacia and is caused by the secretion of fibroblast growth factor 23 (FGF-23) from causative tumors. Scintigraphy with octreotide, which binds to somatostatin receptors (SSTRs), is a useful way to locate causative tumors in OOM patients. However, the therapeutic effects of octreotide acetate are still controversial. Two OOM patients were administered octreotide acetate intramuscularly. Ten causative OOM tumors, including two resected from the patients participating in the octreotide administration study, were examined for expression of genes encoding SSTRs by quantitative real-time RT-PCR and immunohistochemistry. Octreotide therapy did not improve hypophosphatemia in either case, despite temporal decreases in FGF-23 levels in one patient. The mean expression levels of SSTR1, SSTR3, and SSTR5 were similar in the OOM and non-OOM tumors. Expression of SSTR2 was significantly higher in the OOM tumors than in the non-OOM tumors. Immunohistochemical examinations revealed the presence of SSTR2A, SSTR2B, and SSTR5 in both the OOM and non-OOM tumors. The expression of SSTR genes in OOM tumors contributes to positive imaging using octreotide scintigraphy. However, the levels of SSTRs seem to be insufficient for the octreotide therapy to improve hypophosphatemia. Further studies are needed to clarify the mechanisms by which FGF-23 secretion from OOM tumors is suppressed by octreotide acetate.

Slaby O, Sachlova M, Bednarikova M, et al.
Gene expression of somatostatin receptor 4 predicts clinical outcome of patients with metastatic neuroendocrine tumors treated with somatostatin analogs.
Cancer Biother Radiopharm. 2010; 25(2):237-43 [PubMed] Related Publications
Somatostatin analogs (SSA) are the standard diagnostic and treatment tools in the clinical management of patients with neuroendocrine tumors (NETs) expressing somatostatin receptors (SSTRs). Although symptomatic and biochemical control is obtained with SSA in the majority of functional NETs, antineoplastic effects of SSA are partial and of limited duration. The aim of this study was to quantify expression levels of five SSTR subtypes (SSTR1-SSTR5) and correlate them with the clinical outcomes of patients with NETs who underwent SSA therapy. The expression levels were analyzed using real-time polymerase chain reaction in a series of 22 metastatic NETs with a median time of 10 months on the SSA therapy (range 2-82 months). The median duration of disease stabilization in patients who developed progression (n = 14) was 9 months (range 3-92 months). The median survival period for all patients was 44 months (range 3-175 months). According to RECIST criteria, one (5%) partial objective tumor response was obtained, disease stabilization was achieved in 10 (45%) patients, and progressive disease was observed in 11 (50%). Analysis of mRNA expression of the SSTR subtypes showed that SSTR2 and SSTR5 were expressed in all of the studied NETs; SSTR1 and SSTR4 in all but 3 tumors (86%); and SSTR3 in only 10 NETs (49%). Interestingly, our preliminary data suggest that only the levels of SSTR4, though it has the lowest affinity for SSA of all SSTR subtypes, were significantly associated with the stabilization of disease during SSA therapy (p = 0.0357). These levels correlated with time to progression (p = 0.0015) and overall survival (p = 0.0017) in NET patients.

Martinez-Alonso M, Llecha N, Mayorga ME, et al.
Expression of somatostatin receptors in human melanoma cell lines: effect of two different somatostatin analogues, octreotide and SOM230, on cell proliferation.
J Int Med Res. 2009 Nov-Dec; 37(6):1813-22 [PubMed] Related Publications
Somatostatin analogues (SAs) are potential anticancer agents. This study was designed to investigate the expression of somatostatin receptors (SSTRs) in melanoma cells and the effect of two SAs on cell proliferation and viability. Eighteen primary and metastatic human cutaneous melanoma cell lines were treated with octreotide and SOM230. Expression of SSTR1, SSTR2, SSTR3 and SSTR5 was assessed by real-time polymerase chain reaction. Proliferation, viability and cell death were assessed using standard assays. Inhibition was modelled by mixed-effect regression. Melanoma cells expressed one or more SSTR. Both SAs inhibited proliferation of most melanoma cell lines, but inhibition was < 50%. Neither SA affected cell viability or induced cell death. The results suggest that melanoma cell lines express SSTRs. The SAs investigated, under the conditions used in this study, did not, however, significantly inhibit melanoma growth or induce cell death. Novel SAs, combination therapy with SAs and their anti-angiogenic properties should be further investigated.

Klagge A, Krause K, Schierle K, et al.
Somatostatin receptor subtype expression in human thyroid tumours.
Horm Metab Res. 2010; 42(4):237-40 [PubMed] Related Publications
Somatostatin receptors (SSTR) are expressed in various endocrine tumours. The expression of SSTR at the tumour cell surface confers the possibility for diagnostic imaging and therapy of tumours using radiolabeled somatostatin analogues. The majority of currently available somatostatin analogues show a higher binding affinity for the SSTR2 subtype. To date, the precise expression pattern of the SSTR subtypes 1-5 in thyroid epithelial tumours remains to be determined. We investigated the mRNA expression of SSTR1-5 in benign and malignant epithelial thyroid tumours [20 cold thyroid nodules (CTNs), 20 toxic thyroid nodules (TTNs), 20 papillary, 20 follicular, and 5 anaplastic carcinomas (PTCs, FTCs, ATCs, respectively)] and compared them to normal surrounding thyroid tissues. Four out of five SSTR subtypes were detected in malignant thyroid tumours, benign neoplasia, and normal surrounding tissue with a predominant expression of SSTR2 and SSTR5, and a weak expression of SSTR1 and SSTR3. Weak SSTR4 mRNA expression was detected in some PTCs. Compared to normal thyroid tissue, SSTR2 was significantly upregulated in PTC and ATC. In addition significant upregulation of SSTR3 was found in PTC. SSTR5 mRNA expression was increased in PTC and FTC and significantly decreased in CTN and TTN compared to normal thyroid tissue. SSTR2 is the predominant subtype in thyroid epithelial tumours with a high expression pattern, in particular, in PTC . Perspectively, the expression of distinct SSTR in thyroid epithelial tumours might represent a promising avenue for diagnostics and therapy of advanced thyroid cancer with somatostatin analogues.

Johansson M, McKay JD, Wiklund F, et al.
Genetic variation in the SST gene and its receptors in relation to circulating levels of insulin-like growth factor-I, IGFBP3, and prostate cancer risk.
Cancer Epidemiol Biomarkers Prev. 2009; 18(5):1644-50 [PubMed] Related Publications
BACKGROUND: Somatostatin (SST) and its receptors (SSTR1-5) may have a role in prostate cancer by influencing the IGFI hormone axis or through direct effects on prostate epithelia. We have investigated if genetic variation in the SST and SSTR1-5 genes influences prostate cancer risk and/or circulating IGFI and IGFBP3 hormone levels.
MATERIALS AND METHODS: We analyzed 28 haplotype tagging single nucleotide polymorphisms in the SST and SSTR1-5 genes in a case-control/genetic association study to investigate the association between genetic variation and prostate cancer risk. The study included 2863 cases and 1737 controls from the Cancer Prostate in Sweden (CAPS) study. To investigate the genetic influence on circulating hormone levels, plasma concentrations of IGFI and IGFBP3 were analyzed in 874 controls of the CAPS study and 550 male subjects from the Northern Sweden Health and Disease Cohort (NSHDC).
RESULTS: No clear association between prostate cancer risk and genetic variation of the SST and SSTR1-5 genes was identified. The SSTR5 missense single nucleotide polymorphism rs4988483 was associated with circulating IGFI (P = 0.002) and IGFBP3 (P = 0.0003) hormone levels in CAPS controls, with a per allele decrease of approximately 11%. This decrease was replicated in NSHDC for circulating IGFBP3 (P = 0.01) but not for IGFI (P = 0.09). Combining CAPS and NSHDC subjects indicated evidence of association between rs4988483 and both IGFBP3 (P = 2 x 10(-5)) and IGFI (P = 0.0004) hormone levels.
CONCLUSIONS: Our results suggest that genetic variation in the SSTR5 gene and, particularly, the rs4988483 single nucleotide polymorphism influence circulating IGFI and IGFBP3 hormone levels with no measurable effect on prostate cancer risk.

Tateno T, Kato M, Tani Y, et al.
Differential expression of somatostatin and dopamine receptor subtype genes in adrenocorticotropin (ACTH)-secreting pituitary tumors and silent corticotroph adenomas.
Endocr J. 2009; 56(4):579-84 [PubMed] Related Publications
Somatostatin analogs and dopamine agonists are clinically used for medical therapy of functioning pituitary tumors, such as growth hormone- and prolactin-secreting tumors, however, their effects on ACTH-secreting tumors are controversial. This study was aimed to determine whether somatostatin receptor (SSTR) subtype (1-5) and dopamine receptor type 2 (D2R) are differentially expressed in pituitary tumors causing Cushing's disease (CD), silent corticotroph adenoma (SCA), and non-functioning pituitary tumor (NFT). Tissue specimens were obtained from 35 pituitary tumors during transsphenoidal surgery. The steady-state mRNA levels of SSTR1-5 and D2R genes were determined by real-time reverse-transcription polymerase chain reaction. Both SSTR1 and 2 mRNA levels in SCA were greater than CD, while SSTR1 mRNA levels, but not SSTR2, in SCA were also greater than NFT. SSTR5 mRNA levels in CD were greater than SCA, but did not differ between NFT and SCA. SSTR4 mRNA expression was undetectable. D2R mRNA levels were markedly lower in CD and SCA than in NFT. The present study suggests that somatostatin analogs more selective for SSTR5 and for SSTR1 and/or 2may have the therapeutic potential for medical treatment of CD and SCA, respectively, whereas clinical application of dopamine agonists selective for D2R is very limited in either CD or SCA.

Li M, Wang X, Li W, et al.
Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer.
Cancer Sci. 2008; 99(11):2218-23 [PubMed] Free Access to Full Article Related Publications
Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G(0)/G(1) growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n = 5, P < 0.05, Student's t-test), and inhibited tumor weight by 69% and 47% (n = 5, P < 0.05, Student's t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer.

Zhou T, Xiao X, Xu B, et al.
Overexpression of SSTR2 inhibited the growth of SSTR2-positive tumors via multiple signaling pathways.
Acta Oncol. 2009; 48(3):401-10 [PubMed] Related Publications
BACKGROUND: Somatostatin receptors (SSTR1-5) are inhibitory G-protein coupled receptors that are ubiquitously expressed in both normal and cancer cells. Activation of SSTRs results in inhibition of hormone secretion and cell proliferation. Loss-of-expression of SSTR2 in tumor tissues has been suggested to correlate with tumor progression and to the relatively poorer outcomes of somatostatin analog treatment in some clinical trials. Therefore, gene transfer of SSTR2 has been studied extensively in those SSTR2-negative tumors.
MATERIAL AND METHODS: In this research, the anti-proliferation effects of overexpressed SSTR2 were studied in our experimental cancer xenografts with different profiles of endogenous SSTRs expression. An adenoviral vector was used to express full length human SSTR2 in capan-2 and A549 xenografts. The potential pathways involved in SSTR2 signaling were then studied using immunoassays.
RESULTS: Our results showed that overexpression of SSTR2 inhibited the growth of both SSTR2-positive and SSTR2-negative cancer xenografts. The SSTR2-mediated anti-proliferation involved both cytostatic (growth arrest) and cytotoxic (apoptotic) actions by affecting the cellular levels of signaling molecules in apoptotic pathway, MAPK pathway and angiogenesis.
CONCLUSION: SSTR2 inhibits cancer growth via multiple pathways and is a potential candidate for gene therapy for both SSTR2-positive and SSTR2-negative tumors.

Kosari F, Munz JM, Savci-Heijink CD, et al.
Identification of prognostic biomarkers for prostate cancer.
Clin Cancer Res. 2008; 14(6):1734-43 [PubMed] Related Publications
PURPOSE: This paper describes a process for the identification of genes that can report on the aggressiveness of prostate tumors and thereby add to the information provided by current pathologic analysis.
MATERIALS AND METHODS: Expression profiling data from over 100 laser capture microdissection derived samples from nonneoplastic epithelium; Gleason patterns 3, 4, and 5 and node metastasis prostate cancer were used to identify genes at abnormally high levels in only some tumors. These variably overexpressed genes were stratified by their association with aggressive phenotypes and were subsequently filtered to exclude genes with redundant expression patterns. Selected genes were validated in a case-control study in which cases (systemic progression within 5 years) and controls (no systemic progression at 7 years of follow-up) were matched for all clinical and pathologic criteria from time of prostatectomy (n = 175). Both cases and controls, therefore, could have nodal invasion or seminal vesicle involvement at the time of initial treatment.
RESULTS: A number of candidate variably overexpressed genes selected for their association with aggressive prostate cancer phenotype were evaluated in the case control study. The most prominent candidates were SSTR1 and genes related to proliferation, including TOP2A.
CONCLUSIONS: The process described here identified genes that add information not available from current clinical measures and can improve the prognosis of prostate cancer.

Taboada GF, Luque RM, Neto LV, et al.
Quantitative analysis of somatostatin receptor subtypes (1-5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR.
Eur J Endocrinol. 2008; 158(3):295-303 [PubMed] Related Publications
OBJECTIVE: To determine whether the somatostatin receptor subtype (SSTR) expression profile correlates with hormonal and tumor volume responses to postsurgical octreotide long acting repeatable (OCT LAR) treatment.
DESIGN AND METHODS: Quantitative real-time RT-PCR was used to evaluate the absolute mRNA copy numbers for all five SSTR subtypes in 22 somatotropinomas. Response to OCT LAR was studied by hormone levels (GH and IGF-I) and tumor volume (sella turcica magnetic resonance imaging).
RESULTS: SSTR5 was present at the highest level followed by SSTR2, SSTR3, SSTR1, and SSTR4 (2327 (1046-5555), 2098 (194-23 954), 97 (0-460), 14 (0-29 480), and 0 (0-652) copies respectively). Positive correlations were found between SSTR2 levels and the percentage decrease of GH and IGF-I after 3 (r=0.49, P<0.027 and r=0.49, P<0.029 respectively) and 6 (r=0.59, P<0.006 and r=0.58, P<0.008 respectively) months of OCT LAR. A negative correlation was found between SSTR5 mRNA levels and the percentage decrease of GH after 3 months of OCT LAR (r=-0.52, P=0.016, n=21). A higher SSTR2/SSTR5 ratio was observed among patients who obtained hormonal control with OCT LAR, when compared with those uncontrolled (2.4 (0.7-10) vs 0.3 (0.1-7.7), P=0.001). A ROC curve analysis showed a SSTR2/SSTR5 ratio of 1.3 as the best predictor of disease control, with a sensitivity of 88% and a specificity of 92% - area under curve, 0.9. A positive correlation was also found between SSTR2 mRNA levels and the percentage decrease in tumor volume after 6 months of OCT LAR (r=0.79, P=0.002, n=12).
CONCLUSIONS: Somatostatin receptor subtype 2 mRNA expression levels in somatotropinomas correlate positively with in vivo hormonal and tumor volume responses to OCT LAR.

Stec-Michalska K, Peczek Ł, Michalski B, et al.
[Somatostatin receptor subtype 3 (SSTR3) mRNA level in gastric mucosa of patients with dyspepsia].
Pol Merkur Lekarski. 2007; 22(131):341-5 [PubMed] Related Publications
UNLABELLED: Somatostatin (SST) inhibits cellular processes related to secretion, motor activity and cell proliferation. It operates through SSTR1-5 receptors. Density of the SSTR3 receptor is decreased in gastric adenocarcinoma.
AIM: Determination of the SSTR3 mRNA level in gastric mucosa of patients with dyspepsia, in respect to stomach topography, H. pylori infection, patient gender and the type of histopathological changes was aimed in these studies.
MATERIALS AND METHODS: A real time RT-PCR method was used to determine the SSTR3 mRNA level in samples collected from the stomach antrum and corpus of 27 patients with dyspepsia (18-59 years old) without family history of cancer.
RESULTS: Among Hp(-) patients, the level of the SSTR3 mRNA in samples taken from the antrum was by ca. 65% higher (p < 0.05) than from the stomach corpus. Infection with H. pylori significantly decreased the SSTR3 level in antrum (ca. 50%, p < 0.05), especially in females. Among the Hp(+) patients, the development of histopathological changes in that part of stomach was accompanied by decrease of the expression of SSTR3 receptor (p > 0.05).
CONCLUSIONS: H. pylori infection related reduction of the SSTR3 density in the antrum mucosa speaks for the need of eradication of these bacteria in the prevention of distal gastric cancer.

Horiguchi K, Yamada M, Umezawa R, et al.
Somatostatin receptor subtypes mRNA in TSH-secreting pituitary adenomas: a case showing a dramatic reduction in tumor size during short octreotide treatment.
Endocr J. 2007; 54(3):371-8 [PubMed] Related Publications
TSH-secreting adenoma is a rare pituitary adenoma, and the expression levels of the specific subtypes of somatostatin receptors (sstr) mRNAs have remained obscure. To determine the quantitative expression of the sstr1-5 mRNAs in TSH-secreting adenomas that may be related to the efficacy of treatment with a somatostatin analogue, expression of the sstr1-5 mRNAs was examined and compared in TSH-secreting adenomas and other pituitary adenomas. The pituitary adenomas were obtained at transsphenoidal surgery from 4 cases of TSH-secreting adenoma, including 1 patient showing a significant shrinkage of the tumor size after only 10 days of octreotide treatment, 2 patients without tumor size reduction and 1 patient without treatment, and 5 GH-secreting adenomas, 6 prolactinomas, 5 nonfunctioning adenomas, 4 ACTH-secreting adenomas and normal pituitaries at autopsy from 4 normal subjects. In comparison to the normal pituitary, sstr2A>sstr1>sstr5>sstr3 mRNAs were expressed in the TSH-secreting adenomas examined. No expression of sstr2B or sstr4 mRNA was observed. The expression level of sstr2 mRNA was significantly higher than those in normal pituitary, prolactinomas, ACTH-secreting and nonfunctioning pituitary adenomas. The patient with marked shrinkage of the tumor showed the highest expression of both sstr2 and sstr5 mRNAs among all the cases of pituitary adenoma. A TSH-secreting tumor without shrinkage showed a similar expression level of sstr2 mRNA. These findings demonstrated that TSH-secreting adenomas express sstr1, 2A, 3 and 5 mRNAs, predominantly sstr2A, and in addition to the expression of sstr2 mRNA, the expression level of sstr5 mRNA may be a factor affecting the tumor shrinkage by somatostatin analogues against TSH-secreting adenomas.

Taboada GF, Luque RM, Bastos W, et al.
Quantitative analysis of somatostatin receptor subtype (SSTR1-5) gene expression levels in somatotropinomas and non-functioning pituitary adenomas.
Eur J Endocrinol. 2007; 156(1):65-74 [PubMed] Related Publications
OBJECTIVE: It is believed that the variable effectiveness of somatostatin analogs in post-surgical management of somatotropinomas and non-functioning pituitary adenomas (NFPA) may be due in part to variable expression of somatostatin receptor isoforms (SSTR1-5), within and between pituitary tumor types.
DESIGN AND METHODS: Quantitative real-time RT-PCR was used to compare absolute mRNA copy numbers for all five SSTR isoforms in 23 somatotropinomas and 19 NFPA.
RESULTS: Somatostatin receptor subtype 5 mRNA was present at the highest level in somatotropinomas, followed by SSTR2>SSTR3>SSTR1>SSTR4. In contrast, SSTR3 mRNA was present at the highest level in NFPA, followed by SSTR2, while SSTR1, SSTR4, and SSTR5 transcripts were only detectable in select tumors. Among somatotropinomas, a positive correlation was found between SSTR2 mRNA levels and the percent decrease of GH (%GH) after 3 and 6 months of therapy with octreotide long acting repeatable (LAR) (r=0.51 and r=0.66; P=0.05 and P=0.008). Also the percent decrease of IGF-I (%IGF-I) after 3 months of octreotide LAR was negatively correlated with SSTR5 and %IGF-I after 6 months of octreotide LAR was positively correlated with SSTR2.
CONCLUSIONS: The present report is a large series examining SSTR mRNA levels in somatotropinomas and NFPA. These initial findings suggest that detailed knowledge of the SSTR mRNA expression profile in somatotropinomas can help to predict the hormonal response to therapy with LAR. Also, it appears that SSTR3 in NFPA may be a potential target for SSTR3 preferential or universal ligands such as pasireotide.

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