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PMID: 20080953 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cooperative interaction between retinoic acid receptor-alpha and estrogen receptor in breast cancer.

Genes & development ·Vol. 24 ·No. 2 ·2010-01-15 ·Pages 171-82

Ross-Innes CS, Stark R, Holmes KA, Schmidt D, Spyrou C, Russell R, Massie CE, Vowler SL, Eldridge M, Carroll JS

Abstract

Retinoic acid receptor-alpha (RAR alpha) is a known estrogen target gene in breast cancer cells. The consequence of RAR alpha induction by estrogen was previously unknown. We now show that RAR alpha is required for efficient estrogen receptor-alpha (ER)-mediated transcription and cell proliferation. RAR alpha can interact with ER-binding sites, but this occurs in an ER-dependent manner, providing a novel role for RAR alpha that is independent of its classic role. We show, on a genome-wide scale, that RAR alpha and ER can co-occupy regulatory regions together within the chromatin. This transcriptionally active co-occupancy and dependency occurs when exposed to the predominant breast cancer hormone, estrogen--an interaction that is promoted by the estrogen-ER induction of RAR alpha. These findings implicate RAR alpha as an essential component of the ER complex, potentially by maintaining ER-cofactor interactions, and suggest that different nuclear receptors can cooperate for effective transcriptional activity in breast cancer cells.

MeSH Terms
Breast Neoplasms/metabolism DNA/metabolism Estrogens/metabolism Female Gene Expression Regulation, Neoplastic Humans Ligands Protein Binding Receptors, Estrogen/metabolism Receptors, Retinoic Acid/metabolism
Chemicals
Estrogens Ligands Receptors, Estrogen Receptors, Retinoic Acid DNA
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Ross-Innes Caryn S
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge CB2 0RE, United Kingdom.
Stark Rory
Holmes Kelly A
Schmidt Dominic
Spyrou Christiana
Russell Roslin
Massie Charlie E
Vowler Sarah L
Eldridge Matthew
Carroll Jason S
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
1549-5477
DOI
10.1101/gad.552910
Published
2010-01-15
Pages
171-82
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC2807352
Subset
IM
Grants
Cancer Research UK · 15602 · United Kingdom
External Links
PubMed source DOI: 10.1101/gad.552910 PMC Full Text View journal details
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