Gene Summary

Gene:PPP2CB; protein phosphatase 2 catalytic subunit beta
Aliases: PP2CB, PP2Abeta
Summary:This gene encodes the phosphatase 2A catalytic subunit. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. This gene encodes a beta isoform of the catalytic subunit. [provided by RefSeq, Mar 2010]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:serine/threonine-protein phosphatase 2A catalytic subunit beta isoform
Source:NCBIAccessed: 31 August, 2019


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 (1994-2019)
Graph generated 31 August 2019 using data from PubMed using criteria.

Literature Analysis

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Tag cloud generated 31 August, 2019 using data from PubMed, MeSH and CancerIndex

Latest Publications: PPP2CB (cancer-related)

Bott A, Erdem N, Lerrer S, et al.
miRNA-1246 induces pro-inflammatory responses in mesenchymal stem/stromal cells by regulating PKA and PP2A.
Oncotarget. 2017; 8(27):43897-43914 [PubMed] Free Access to Full Article Related Publications
The tumor microenvironment (TME) has an impact on breast cancer progression by creating a pro-inflammatory milieu within the tumor. However, little is known about the roles of miRNAs in cells of the TME during this process. We identified six putative oncomiRs in a breast cancer dataset, all strongly correlating with poor overall patient survival. Out of the six candidates, miR-1246 was upregulated in aggressive breast cancer subtypes and expressed at highest levels in mesenchymal stem/stroma cells (MSCs). Functionally, miR-1246 led to a p65-dependent increase in transcription and release of pro-inflammatory mediators IL-6, CCL2 and CCL5 in MSCs, and increased NF-κB activity. The pro-inflammatory phenotype of miR-1246 in MSCs was independent of TNFα stimulations and mediated by direct targeting of the tumor-suppressors PRKAR1A and PPP2CB. In vitro recapitulation of the TME revealed increased Stat3 phosphorylation in breast epithelial (MCF10A) and cancer cells (SK-BR-3, MCF7, T47D) upon incubation with conditioned medium (CM) of MSCs overexpressing miR-1246. Additionally, this stimulation enhanced proliferation of MCF10A cells, increased migration of MDA-MB-231 cells and induced attraction of THP-1 monocytic cells. Our data shows that miR-1246 acts as both key-enhancer of pro-inflammatory responses in MSCs and putative oncomiR in breast cancer, suggesting its influence on cancer-related inflammation and breast cancer progression.

El-Heliebi A, Kroneis T, Wagner K, et al.
Resolving tumor heterogeneity: genes involved in chordoma cell development identified by low-template analysis of morphologically distinct cells.
PLoS One. 2014; 9(2):e87663 [PubMed] Free Access to Full Article Related Publications
The classical sacrococcygeal chordoma tumor presents with a typical morphology of lobulated myxoid tumor tissue with cords, strands and nests of tumor cells. The population of cells consists of small non-vacuolated cells, intermediate cells with a wide range of vacuolization and large heavily vacuolated (physaliferous) cells. To date analysis was only performed on bulk tumor mass because of its rare incidence, lack of suited model systems and technical limitations thereby neglecting its heterogeneous composition. We intended to clarify whether the observed cell types are derived from genetically distinct clones or represent different phenotypes. Furthermore, we aimed at elucidating the differences between small non-vacuolated and large physaliferous cells on the genomic and transcriptomic level. Phenotype-specific analyses of small non-vacuolated and large physaliferous cells in two independent chordoma cell lines yielded four candidate genes involved in chordoma cell development. UCHL3, coding for an ubiquitin hydrolase, was found to be over-expressed in the large physaliferous cell phenotype of MUG-Chor1 (18.7-fold) and U-CH1 (3.7-fold) cells. The mannosyltransferase ALG11 (695-fold) and the phosphatase subunit PPP2CB (18.6-fold) were found to be up-regulated in large physaliferous MUG-Chor1 cells showing a similar trend in U-CH1 cells. TMEM144, an orphan 10-transmembrane family receptor, yielded contradictory data as cDNA microarray analysis showed up- but RT-qPCR data down-regulation in large physaliferous MUG-Chor1 cells. Isolation of few but morphologically identical cells allowed us to overcome the limitations of bulk analysis in chordoma research. We identified the different chordoma cell phenotypes to be part of a developmental process and discovered new genes linked to chordoma cell development representing potential targets for further research in chordoma tumor biology.

Loo LW, Tiirikainen M, Cheng I, et al.
Integrated analysis of genome-wide copy number alterations and gene expression in microsatellite stable, CpG island methylator phenotype-negative colon cancer.
Genes Chromosomes Cancer. 2013; 52(5):450-66 [PubMed] Free Access to Full Article Related Publications
Microsatellite stable (MSS), CpG island methylator phenotype (CIMP)-negative colorectal tumors, the most prevalent molecular subtype of colorectal cancer, are associated with extensive copy number alteration (CNA) events and aneuploidy. We report on the identification of characteristic recurrent CNA (with frequency >25%) events and associated gene expression profiles for a total of 40 paired tumor and adjacent normal colon tissues using genome-wide microarrays. We observed recurrent CNAs, namely gains at 1q, 7p, 7q, 8p12-11, 8q, 12p13, 13q, 20p, 20q, Xp, and Xq and losses at 1p36, 1p31, 1p21, 4p15-12, 4q12-35, 5q21-22, 6q26, 8p, 14q, 15q11-12, 17p, 18p, 18q, 21q21-22, and 22q. Within these genomic regions we identified 356 genes with significant differential expression (P < 0.0001 and ±1.5-fold change) in the tumor compared to adjacent normal tissue. Gene ontology and pathway analyses indicated that many of these genes were involved in functional mechanisms that regulate cell cycle, cell death, and metabolism. An amplicon present in >70% of the tumor samples at 20q11-20q13 contained several cancer-related genes (AHCY, POFUT1, RPN2, TH1L, and PRPF6) that were upregulated and demonstrated a significant linear correlation (P < 0.05) for gene dosage and gene expression. Copy number loss at 8p, a CNA associated with adenocarcinoma and poor prognosis, was observed in >50% of the tumor samples and demonstrated a significant linear correlation for gene dosage and gene expression for two potential tumor suppressor genes, MTUS1 (8p22) and PPP2CB (8p12). The results from our integration analysis illustrate the complex relationship between genomic alterations and gene expression in colon cancer.

Yuan Q, Li PD, Li BH, et al.
Differential IL-4/Stat6 activities correlate with differential expression of regulatory genes SOCS-1, SHP-1, and PP2A in colon cancer cells.
J Cancer Res Clin Oncol. 2009; 135(1):131-40 [PubMed] Related Publications
PURPOSE: To investigate potential differences in the expression of Stat6 regulatory genes that may influence IL-4/Stat6 activities (phenotypes) in colon cancer cells.
METHODS: RT-PCR method was employed to examine the constitutive mRNA expression of Stat6 negative regulators SOCS-1 and SHP-1, and positive regulator PP2A in colon cancer cell lines HT-29 and Caco-2. Stat6 protein expression and nuclear phosphorylation were detected using Western blotting.
RESULTS: Caco-2 cells carrying inactive Stat6(null) phenotype showed normal constitutive expression of Stat6 but decreased phosphorylation of nuclear Stat6 compared with HT-29 cells carrying active Stat6(high) phenotype. Stat6(null) Caco-2 cells expressed increased levels of mRNA and protein of SOCS-1 and SHP-1, and decreased mRNA expression of PPP2CA and PPP2CB, encoding two critical subunits of PP2A.
CONCLUSIONS: Constitutively increased expression of Stat6 negative regulators SOCS-1 and SHP-1, together with decreased expression of positive regulator PP2A, may play a role in forming the inactive Stat6(null) phenotype in colon cancer cells.

Hornstein M, Hoffmann MJ, Alexa A, et al.
Protein phosphatase and TRAIL receptor genes as new candidate tumor genes on chromosome 8p in prostate cancer.
Cancer Genomics Proteomics. 2008 Mar-Apr; 5(2):123-36 [PubMed] Related Publications
BACKGROUND: Allelic losses on chromosome 8p are common in prostate carcinoma, but it is not known exactly how they contribute to cancer development and progression.
MATERIALS AND METHODS: Expression of 12 genes located across chromosome 8p, including established tumor suppressor candidates (CSMD1, DLC1, NKX3.1), and others from a new microarray-based comparison was studied by quantitative RT-PCR in 45 M0 prostate carcinomas and 13 benign prostate tissues.
RESULTS: Significantly reduced expression was observed for two protein phosphatase subunit genes (PPP2CB, PPP3CC) and two TRAIL decoy receptors (TNFRSF10C/DcR1, TNFRSF10D/DcR2), but not for the three established candidates nor for TRAIL death receptor genes. Low expression of PPP3CC and TNFRSF10C located at 8p21.3 was highly significantly associated with tumor recurrence. In addition to allele loss, down-regulation of TNFRSF10C and TNFRSF10D was found to be associated with hypermethylation, although bisulfite sequencing usually revealed it to be partial.
CONCLUSION: Our data strongly support a recent proposal that a segment at 8p21.3 contains crucial prostate cancer tumor suppressors. In addition, they raise the paradoxical issue of why TRAIL decoy receptors rather than death receptors are down-regulated in aggressive prostate cancer.

Prowatke I, Devens F, Benner A, et al.
Expression analysis of imbalanced genes in prostate carcinoma using tissue microarrays.
Br J Cancer. 2007; 96(1):82-8 [PubMed] Free Access to Full Article Related Publications
To identify candidate genes relevant for prostate tumour prognosis and progression, we performed an exhaustive gene search in seven previously described genomic-profiling studies of 161 prostate tumours, and four expression profiling studies of 61 tumours. From the resulting list of candidate genes, six were selected for protein-expression analysis based on the availability of antibodies applicable to paraffinised tissue: fatty acid synthase (FASN), MYC, beta-adrenergic receptor kinase 1 (BARK1, GRK2) the catalytic subunits of protein phosphatases PP1alpha (PPP1CA) and PP2A (PPP2CB) and metastasis suppressor NM23-H1. These candidates were analysed by immunohistochemistry (IHC) on a tissue microarray containing 651 cores of primary prostate cancer samples and benign prostatic hyperplasias (BPH) from 175 patients. In univariate analysis, expression of PP1alpha (P=0.001) was found to strongly correlate with Gleason score. MYC immunostaining negatively correlated with both pT-stage and Gleason score (P<0.001 each) in univariate as well as in multivariate analysis. Furthermore, a subgroup of patients with high Gleason scores was characterised by a complete loss of BARK1 protein (P=0.023). In conclusion, our study revealed novel molecular markers of potential diagnostic and therapeutic relevance for prostate carcinoma.

Wissmann C, Wild PJ, Kaiser S, et al.
WIF1, a component of the Wnt pathway, is down-regulated in prostate, breast, lung, and bladder cancer.
J Pathol. 2003; 201(2):204-12 [PubMed] Related Publications
To detect novel Wnt-pathway genes involved in tumourigenesis, this study analysed the RNA expression levels of 40 genes of the Wnt pathway by chip hybridization of microdissected matched pairs of 54 primary prostate carcinomas. Eleven genes showed greater than two-fold differential expression in at least 10% of prostate cancers. Three of these genes encode extracellular components of the Wnt pathway (WNT2, WIF1, SFRP4); two are receptors (FZD4, FZD6); two belong to the intracellular signal cascade (DVL1, PPP2CB); one regulates transcription (TCF4); and three represent genes regulated by this pathway (CCND2, CD44, MYC). While SFRP4, FZD4, FZD6, DVL1, TCF4, and MYC are up-regulated, WIF1, WNT2, PPP2CB, CCND2, and CD44 are down-regulated in certain prostate cancer patients. Wnt inhibitory factor 1 (WIF1) and secreted frizzled related protein (SFRP4) showed the most significant aberrant expression at the RNA level. WIF1 was down-regulated in 64% of primary prostate cancers, while SFRP4 was up-regulated in 81% of the patients. Immunohistochemical analysis using a polyclonal antibody revealed strong cytoplasmic perinuclear WIF1 expression in normal epithelial cells of the prostate, breast, lung, and urinary bladder. Strong reduction of WIF1 protein expression was found in 23% of prostate carcinomas, but also in 60% of breast, 75% of non-small cell lung (NSCLC), and 26% of bladder cancers analysed. No significant association between WIF1 down-regulation and tumour stage or grade was observed for prostate, breast or non-small cell lung carcinomas, indicating that loss of WIF1 expression may be an early event in tumourigenesis in these tissues. However, down-regulation of WIF1 correlated with higher tumour stage in urinary bladder tumours (pTa versus pT1-pT4; p = 0.038).

Eydmann ME, Knowles MA
Mutation analysis of 8p genes POLB and PPP2CB in bladder cancer.
Cancer Genet Cytogenet. 1997; 93(2):167-71 [PubMed] Related Publications
The DNA polymerase beta gene (POLB), which encodes a DNA polymerase believed to be involved in short gap-filling DNA synthesis, has been mapped to the proximal region of 8p (8p12-p11), a region commonly deleted in bladder carcinoma and a wide variety of other neoplasms. Also mapped to this region (8p12-p11.2) is the gene encoding the beta isoform of the catalytic subunit of protein phosphatase 2A (PPP2CB), a major serine/threonine phosphatase thought to play a regulatory role in many cellular pathways. The known functions of these proteins make them good candidates for 8p tumor suppressor genes. To test this hypothesis, we assessed a series of bladder tumors and bladder tumor cell lines for sequence variation in POLB and PPP2CB. Single strand conformation polymorphism (SSCP) analysis and direct sequencing of POLB cDNA derived from cell lines and tumors, many with known deletions of proximal 8p, revealed one sequence variant that was shown to represent a normal sequence polymorphism. No tumor-specific sequence variants were identified. The promotor sequence in genomic DNA from tumors with 8p LOH was also screened by SSCP. Four polymorphisms were identified but no tumor-specific mutations were found. PPP2CB was analyzed by SSCP analysis of all 7 coding exons in genomic DNA of bladder tumors and cell lines. Polymorphisms were detected in exons 4 and 5 but no tumor-specific mutations were found. We conclude that these genes are unlikely to be the suppressor genes for bladder cancer targeted by deletions of chromosome arm 8p.

Imbert A, Chaffanet M, Essioux L, et al.
Integrated map of the chromosome 8p12-p21 region, a region involved in human cancers and Werner syndrome.
Genomics. 1996; 32(1):29-38 [PubMed] Related Publications
Detailed physical maps of the human genome are important resources for the identification and isolation of disease genes and for studying the structure and function of the genome. To improve the definition of the 8p12-p21 chromosomal region, an integrated physical and genetic map was constructed extending from the genes. NEFL to FGFR1. The map comprises a series of contigs (the larger of these being around 9 Mb) of yeast artificial chromosomes (YACs) spanning the proximal region of deletion involved in a broad range of human cancers, including breast carcinomas, and in the Werner syndrome. In addition, losses of heterozygosity at 8p markers and linkage analysis of breast cancer families were also detailed. Finally, several genes potentially involved in 8p-associated diseases, namely GTF2E2, PPP2CB, and HGL, were precisely mapped within the YAC contigs. The reported map and contigs of YACs should facilitate the search for putative genes involved in sporadic and familial breast cancer as well as in the Werner syndrome.

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Cite this page: Cotterill SJ. PPP2CB, Cancer Genetics Web: http://www.cancer-genetics.org/PPP2CB.htm Accessed:

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