title: Complex formation and function of estrogen receptor α in transcription requires RIP140.
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.
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Rosell
authors.affiliation: Division of Molecular Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands. Division of Molecular Carcinogenesis, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Nevedomskaya
authors.affiliation: Division of Molecular Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Suzan
authors.initials: S
authors.lastname: Stelloo
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: Jaya
authors.initials: J
authors.lastname: Nautiyal
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: Ariel
authors.initials: A
authors.lastname: Poliandri
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Steel
authors.affiliation: Division of Molecular Carcinogenesis, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Lodewyk F A
authors.initials: LF
authors.lastname: Wessels
authors.affiliation: Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Carroll
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: Malcolm G
authors.initials: MG
authors.lastname: Parker
authors.affiliation: Division of Molecular Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands. w.zwart@nki.nl.
authors.forename: Wilbert
authors.initials: W
authors.lastname: Zwart
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000502:physiology*; D006801:Humans; D061986:MCF-7 Cells; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D000078723:Nuclear Receptor Interacting Protein 1; D011485:Protein Binding; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002843:Chromatin; D047628:Estrogen Receptor alpha; C000627127:NRIP1 protein, human; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1