Co-operative interaction between Retinoic Acid Receptor-a and Estrogen Receptor in breast cancer

Retinoic Acid Receptor-a (RARa) is a known estrogen target gene in breast cancer cells. The consequence of RARa induction by estrogen was previously unknown. We now show that RARa is required for efficient Estrogen Receptor-a (ER)-mediated transcription and cell proliferation. RARa can interact with ER binding regions, but this occurs in an ER-dependent manner, providing a novel role for RARa that is independent of its classic role. We show, on a genome-wide scale, that RARa 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 RARa. These findings implicate RARa as an essential component of the ER complex, potentially by maintaining ER-co-factor interactions and suggest that different nuclear receptors can co-operate for effective transcriptional activity in breast cancer cells.