Cited by 410Estrogen and related hormone effectsBreast Cancer Treatment StudiesGenomics and Chromatin Dynamics

Endogenous Purification Reveals GREB1 as a Key Estrogen Receptor Regulatory Factor

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Mohammed, Hisham, D’Santos, Clive, Serandour, Aurelien A., Ali, H. Raza, Brown, Gordon D., Atkins, Alan, Rueda, Oscar M., Holmes, Kelly A. +11 more·2013·Cell Reports

Abstract

Estrogen receptor-α (ER) is the driving transcription factor in most breast cancers, and its associated proteins can influence drug response, but direct methods for identifying interacting proteins have been limited. We purified endogenous ER using an approach termed RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins) and discovered the interactome under agonist- and antagonist-liganded conditions in breast cancer cells, revealing transcriptional networks in breast cancer. The most estrogen-enriched ER interactor is GREB1, a potential clinical biomarker with no known function. GREB1 is shown to be a chromatin-bound ER coactivator and is essential for ER-mediated transcription, because it stabilizes interactions between ER and additional cofactors. We show a GREB1-ER interaction in three xenograft tumors, and using a directed protein-protein approach, we find GREB1-ER interactions in half of ER(+) primary breast cancers. This finding is supported by histological expression of GREB1, which shows that GREB1 is expressed in half of ER(+) cancers, and predicts good clinical outcome. These findings reveal an unexpected role for GREB1 as an estrogen-specific ER cofactor that is expressed in drug-sensitive contexts.

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Authors
Mohammed, H., D’Santos, C., Serandour, A. A., Ali, H. R., Brown, G. D., Atkins, A., Rueda, O. M., Holmes, K. A., Theodorou, V., Robinson, J. L. L., Zwart, W., Saadi, A., Ross-Innes, C. S., Chin, S.-F., Menon, S., Stingl, J., Palmieri, C., Caldas, C., & Carroll, J. S.
Affiliations
  • Cancer Research UK (GB)
  • Thermo Fisher Scientific (United Kingdom) (GB)
  • Imperial College Healthcare NHS Trust (GB)
  • University of Cambridge (GB)
Corresponding author
Carroll, Jason S.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2013-02
Volume
3
Issue
2
Pages
342-349
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2135060880
Cited by
400
References
50
Citations by year
2026: 22 · 2025: 20 · 2024: 25 · 2023: 40 · 2022: 28 · 2021: 28 · 2020: 29 · 2019: 42 · 2018: 37 · 2017: 40 · 2016: 35 · 2015: 26 · 2014: 18 · 2013: 10
FWCI
19.68
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
  • Apollo
Funders
  • Cancer Research UK (A20411, 10208, 15602, 22310)
  • National Institute for Health and Care Research (CL-2013-14-006)
  • Imperial College London
  • Imperial College Healthcare NHS Trust
  • Hutchison Whampoa Limited
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
GREB1, estrogen receptor alpha, protein-protein interaction, breast cancer, estrogen receptor coactivator, transcriptional regulation, Rime, estrogen receptor-positive breast cancer, clinical biomarkers, drug response
MeSH terms
Animals, Breast Neoplasms, Chromatin, Female, Humans, Neoplasm Proteins, Transcription, Genetic, Transplantation, Heterologous, Gene Expression Regulation, Neoplastic, Mice, SCID, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Chromatin Immunoprecipitation, Estrogen Receptor alpha, Mice, Protein Interaction Maps, MCF-7 Cells

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