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ERα-CtBP-mediated repression of Homologous-recombination repair in ovarian cancer improves chemo-sensitivity [RNA-seq]

ABSTRACT: Deficiency in homologous recombination repair (HRR) is frequently associated with hormone-responsive cancers. Epithelial ovarian cancer (EOC) is a typical hormone-related tumor, with defects of HRR in up to half of cases. However, whether there are molecular connections between estrogen signaling and HRR deficiency in EOC remains unknown. Here we report an inverse correlation between estrogen signaling and HRR activity in EOC. Genome-wide mapping of ERα reveals ERα co-bindings with co-repressor CtBP, especially on many HRR gene loci, in EOC cells but not in breast cancer cells. Consistently, depleting ERα in EOC cells up-regulates HRR activity and HRR gene expression. Importantly, estrogen signaling enhances the sensitivity of ovarian cancer cells to chemotherapy agents in vitro and in vivo. Large-scale analyses further indicate that estrogen replacement and ERα expression are associated with favorable survival of EOC patients. These findings characterize a novel role of ERα in mediating the molecular connection between hormone and HRR in EOC, and suggest that estrogen signaling may improve the treatment outcome of EOC patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE115481 | GEO | 2019/06/26

REPOSITORIES: GEO

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ERα-CtBP-mediated repression of Homologous-recombination repair in ovarian cancer improves chemo-sensitivity [ChIP-seq]

Project description:Deficiency in homologous recombination repair (HRR) is frequently associated with hormone-responsive cancers. Epithelial ovarian cancer (EOC) is a typical hormone-related tumor, with defects of HRR in up to half of cases. However, whether there are molecular connections between estrogen signaling and HRR deficiency in EOC remains unknown. Here we report an inverse correlation between estrogen signaling and HRR activity in EOC. Genome-wide mapping of ERα reveals ERα co-bindings with co-repressor CtBP, especially on many HRR gene loci, in EOC cells but not in breast cancer cells. Consistently, depleting ERα in EOC cells up-regulates HRR activity and HRR gene expression. Importantly, estrogen signaling enhances the sensitivity of ovarian cancer cells to chemotherapy agents in vitro and in vivo. Large-scale analyses further indicate that estrogen replacement and ERα expression are associated with favorable survival of EOC patients. These findings characterize a novel role of ERα in mediating the molecular connection between hormone and HRR in EOC, and suggest that estrogen signaling may improve the treatment outcome of EOC patients.

2019-06-26 | GSE116005 | GEO

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ERα-CtBP-mediated repression of Homologous-recombination repair in ovarian cancer improves chemo-sensitivity

Project description:ERα-CtBP-mediated repression of Homologous-recombination repair in ovarian cancer improves chemo-sensitivity

| PRJNA476796 | ENA

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