Complex formation and function of estrogen receptor α in transcription requires RIP140.
Cancer Res
; 74(19): 5469-79, 2014 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-25145671
ABSTRACT
RIP140 is a transcriptional coregulator involved in energy homeostasis, ovulation, and mammary gland development. Although conclusive evidence is lacking, reports have implicated a role for RIP140 in breast cancer. Here, we explored the mechanistic role of RIP140 in breast cancer and its involvement in estrogen receptor α (ERα) transcriptional regulation of gene expression. Using ChIP-seq analysis, we demonstrate that RIP140 shares more than 80% of its binding sites with ERα, colocalizing with its interaction partners FOXA1, GATA3, p300, CBP, and p160 family members at H3K4me1-demarcated enhancer regions. RIP140 is required for ERα-complex formation, ERα-mediated gene expression, and ERα-dependent breast cancer cell proliferation. Genes affected following RIP140 silencing could be used to stratify tamoxifen-treated breast cancer cohorts, based on clinical outcome. Importantly, this gene signature was only effective in endocrine-treated conditions. Cumulatively, our data suggest that RIP140 plays an important role in ERα-mediated transcriptional regulation in breast cancer and response to tamoxifen treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Proteínas Nucleares
/
Proteínas Adaptadoras de Transdução de Sinal
/
Receptor alfa de Estrogênio
Limite:
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Reino Unido