Dataset Information

PES1 promotes breast cancer by differentially regulating ER? and ER?.

ABSTRACT: The initiation of breast cancer is associated with increased expression of tumor-promoting estrogen receptor ? (ER?) protein and decreased expression of tumor-suppressive ER? protein. However, the mechanism underlying this process is unknown. Here we show that PES1 (also known as Pescadillo), an estrogen-inducible protein that is overexpressed in breast cancer, can regulate the balance between ER? and ER?. We found that PES1 modulated many estrogen-responsive genes by enhancing the transcriptional activity of ER? while inhibiting transcriptional activity of ER?. Consistent with this regulation of ER? and ER? transcriptional activity, PES1 increased the stability of the ER? protein and decreased that of ER? through the ubiquitin-proteasome pathway, mediated by the carboxyl terminus of Hsc70-interacting protein (CHIP). Moreover, PES1 transformed normal human mammary epithelial cells and was required for estrogen-induced breast tumor growth in nude mice. Further analysis of clinical samples showed that expression of PES1 correlated positively with ER? expression and negatively with ER? expression and predicted good clinical outcome in breast cancer. Our data demonstrate that PES1 contributes to breast tumor growth through regulating the balance between ER? and ER? and may be a better target for the development of drugs that selectively regulate ER? and ER? activities.

SUBMITTER: Cheng L

PROVIDER: S-EPMC3408741 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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PES1 promotes breast cancer by differentially regulating ERα and ERβ.

Cheng Long L Li Jieping J Han Yongjian Y Lin Jing J Niu Chang C Zhou Zhichao Z Yuan Bin B Huang Ke K Li Jiezhi J Jiang Kai K Zhang Hao H Ding Lihua L Xu Xiaojie X Ye Qinong Q

The Journal of clinical investigation 20120723 8

The initiation of breast cancer is associated with increased expression of tumor-promoting estrogen receptor α (ERα) protein and decreased expression of tumor-suppressive ERβ protein. However, the mechanism underlying this process is unknown. Here we show that PES1 (also known as Pescadillo), an estrogen-inducible protein that is overexpressed in breast cancer, can regulate the balance between ERα and ERβ. We found that PES1 modulated many estrogen-responsive genes by enhancing the transcription ...[more]

PMID: 22820289

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Project description:BackgroundTreatment strategies for various subtypes of breast cancer (BC) are different based on their distinct molecular characteristics. Therefore, it is very important to identify key differentially expressed genes (DEGs) between ER-positive/HER2-negative BC and ER-negative/HER2-negative BC.MethodsGene expression profiles of GSE22093 and GSE23988 were obtained from the Gene Expression Omnibus database. There were 74 ER-positive/HER2-negative BC tissues and 85 ER-negative/HER2-negative BC tissues in the two profile datasets. DEGs between ER-positive/HER2-negative tissues and ER-negative/HER2-negative BC tissues were identified by the GEO2R tool. The common DEGs among the two datasets were detected with Venn software online. Next, we made use of the Database for Annotation, Visualization and Integrated Discovery to analyze enriched Kyoto Encyclopedia of Gene and Genome (KEGG) pathways and gene ontology terms. Then, the protein-protein interactions (PPIs) of these DEGs were visualized by Cytoscape with the Search Tool for the Retrieval of Interacting Genes. Of the proteins in the PPI network, Molecular Complex Detection plug-in analysis identified nine core upregulated genes and one core downregulated gene. UALCAN and Gene Expression Profiling Interactive Analysis were applied to determine the expression of these 10 genes in BC. Furthermore, for the analysis of overall survival among those genes, the Kaplan-Meier method was implemented.ResultsNinety-three common DEGs (63 upregulated and 30 downregulated) were identified. KEGG pathway enrichment analysis showed that upregulated DEGs were particularly enriched in the progesterone-mediated oocyte maturation pathway. In addition, PGR might be a prognostic biomarker for ER-positive/HER2-negative BC. CCND1 is a poor prognostic biomarker for ER-positive/HER2-negative BC and ER-negative/HER2-negative BC. Moreover, TFF1, AGR2 and EGFR might be predictive biomarkers of node metastasis in ER-positive/HER2-negative BC and ER-negative/HER2-negative BC.ConclusionsCCND1, AGR2, PGR, TFF1 and EGFR are the key DEGs between ER-positive/HER2-negative BC and ER-negative/HER2-negative BC. Further studies are required to confirm the functions of the identified genes.

Dataset Information

PES1 promotes breast cancer by differentially regulating ER? and ER?.

Publications

PES1 promotes breast cancer by differentially regulating ERα and ERβ.

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