Transcriptional effect of CRH on MCF7 estrogen receptor signalling
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Lal S
PROVIDER: S-ECPF-GEOD-47958 | biostudies-other | 2013 Jul
REPOSITORIES: biostudies-other
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Project description:MCF7 cells were stimulated with vehicle or 100nM corticotropin releasing hormone (CRH) for 24h. The effect of CRH on the expression of genes relevant to estrogen signalling was investigated by using the Human Estrogen Receptor Signaling RTM-BM-2 ProfilerM-bM-^DM-" PCR Array (SABioscience Corp). qPCR gene expression profiling. MCF7 cells were treated separately in triplicate. Equal amount total RNA was processed further for gene expression analysis.
2013-07-02 | E-GEOD-47958 | biostudies-arrayexpress
Project description:MCF7 cells were stimulated with vehicle or 100nM corticotropin releasing hormone (CRH) for 24h. The effect of CRH on the expression of genes relevant to estrogen signalling was investigated by using the Human Estrogen Receptor Signaling RT² Profiler™ PCR Array (SABioscience Corp).
2013-07-02 | GSE47958 | GEO
Project description:An increasing body of evidence now links estrogenic signalling with the metabolic syndrome (MS). Despite the beneficial estrogenic effects in reversing some of the MS symptoms, the underlying mechanisms remain largely undiscovered. We have previously shown that total estrogen receptor alpha (ER?) knockout (KO) mice exhibit hepatic insulin resistance. To determine whether liver-selective ablation of ER? recapitulates metabolic phenotypes of ERKO mice we generated a liver-selective ER?KO mouse model, LERKO. We demonstrate that LERKO mice have efficient reduction of ER? selectively within the liver. However, LERKO and wild type control mice do not differ in body weight, and have a comparable hormone profile as well as insulin and glucose response, even when challenged with a high fat diet. Furthermore, LERKO mice display very minor changes in their hepatic transcript profile. Collectively, our findings indicate that hepatic ER? action may not be the responsible factor for the previously identified hepatic insulin resistance in ER?KO mice.
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Project description:Estrogen receptor-? (ER?) and transforming growth factor-beta (TGF-?) signaling pathways are essential regulators during mammary gland development and tumorigenesis. Ski-related novel gene (SnoN) is an oncoprotein and a negative feedback inhibitor of TGF-? signaling. We have previously reported that low expression of SnoN in ER? positive breast carcinomas is associated with favorable prognosis (Zhang et al. Cancer Res. (2003) 63, 5005-5010). Here we have studied the mechanism of a possible cross-talk between ER? and SnoN. We find that SnoN interacts with the estrogen-activated form of ER? in the nucleus. SnoN contains two highly conserved nuclear receptor binding LxxLL-like motifs and we show that mutations in these motifs reduce the interaction of SnoN with ER?. Over-expression of SnoN enhanced the transcriptional activity of ER? in estrogen response element (ERE)-reporter assays, augmented the expression of several ER? target genes and increased the proliferation of MCF7 breast carcinoma cells in an estrogen-dependent manner. Chromatin immunoprecipitation demonstrated that SnoN interacts with ER? at the TTF1 (pS2) gene promoter. Conversely, silencing of SnoN reduced both ERE-reporter activity and the expression of ER? target genes in MCF7 and T-47D breast cancer cells. Histone deacetylase inhibition increased the level of SnoN and SnoN-dependent enhancement of ER?-dependent transcription and SnoN supported the recruitment of p300 histone acetylase to ER?. This study reveals a novel mechanism that interconnects ER? and TGF-? signaling pathways by SnoN. Accordingly, the results indicate that high SnoN level promotes ER? signaling and possibly breast cancer progression.
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Project description:[This corrects the article DOI: 10.1371/journal.pone.0057458.].
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