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Supplementary Figure S3 from Complex Formation and Function of Estrogen Receptor α in Transcription Requires RIP140

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posted on 2023-03-30, 23:00 authored by Meritxell Rosell, Ekaterina Nevedomskaya, Suzan Stelloo, Jaya Nautiyal, Ariel Poliandri, Jennifer H. Steel, Lodewyk F.A. Wessels, Jason S. Carroll, Malcolm G. Parker, Wilbert Zwart

Supplementary Figure S3. siRNA targeting of RIP140.

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ARTICLE 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. Cancer Res; 74(19); 5469–79. ©2014 AACR.