Endogenous coactivator ARA70 interacts with estrogen receptor α (ERα) and modulates the functional ERα/androgen receptor interplay in MCF-7 cells

Abstract

Overexpression of androgen receptor (AR) decreases estrogen receptor α (ERα) transactivation, which plays a basic role in hormone-dependent breast cancer. This transcriptional interference can be due to shared coactivators. Here we demonstrated that in MCF-7 cells ARA70, an AR-specific coactivator, interacted with endogenous ERα, increasing its transcriptional activity, and it was recruited to the pS2 gene promoter. Moreover, a dominant negative ARA70 down-regulated ERα transcriptional activity as well as pS2 mRNA. ARA70 overexpression reversed the AR down-regulatory effect on ERα signaling. However, in the presence of a progressive increase of transfected AR, ARA70 switched into enhancing the inhibitory effect of AR on ERα signaling. These opposite effects of ARA70 were further evidenced by coimmunoprecipitation assay in MCF-7wt, MCF-7-overexpressing AR, and HeLa cells, exogenously expressing an excess of ERα with respect to AR or an excess of AR with respect to ERα. Thus, ARA70 is a coactivator for ERα and may represent a functional link between ERα/AR modulating their cross-talk in models of estrogen signaling in MCF-7 and HeLa cells. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.