Cooperative Interaction Between Retinoic Acid Receptor-alpha and Estrogen Receptor in Breast Cancer

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2010 Jan 19

PMID 20080953

Citations 138

Authors

Caryn S Ross-Innes

Rory Stark

Kelly A Holmes

Dominic Schmidt

Christiana Spyrou

Roslin Russell

Charlie E Massie

Sarah L Vowler

Matthew Eldridge

Jason S Carroll

Affiliations

Soon will be listed here.

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.

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