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

Abstract

Retinoic acid receptor-α (RARα) is a known estrogen target gene in breast cancer cells. The consequence of RARα induction by estrogen was previously unknown. We now show that RARα is required for efficient estrogen receptor-α (ER)-mediated transcription and cell proliferation. RARα can interact with ER-binding sites, but this occurs in an ER-dependent manner, providing a novel role for RARα that is independent of its classic role. We show, on a genome-wide scale, that RARα 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 RARα. These findings implicate RARα 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.