Authors:
M Rosell, E Nevedomskaya, S Stelloo, J Nautiyal, A Poliandri, JH Steel, LFA Wessels, JS Carroll, MG Parker, W Zwart
Journal name: 
Cancer Res
Citation info: 
74(19):5469-5479
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.
DOI: 
http://doi.org/10.1158/0008-5472.CAN-13-3429
Research group: 
Carroll Group
E-pub date: 
01 Oct 2014