Suppression by estrogen receptor beta of AP-1 mediated transactivation through estrogen receptor alpha

The estrogen receptor (ER) is known to mediate gene transcription from AP-1 enhancer elements as well as the well-documented estrogen responsive eleme nts (EREs). Investigations of AP-1 mediated transactivation through ER have been performed with rather complex promoters such as insulin like growth f actor I (IGF-1) and collagenase promoters, In the present study, we investi gated AP-1 mediated transactivation through ER alpha and ER beta with a les s complicated reporter consisting of only consensus AP-1 motifs. NIH 3T3 ce lls were transiently transfected with human ER alpha and ER beta expression plasmids and AP-1-luc and ERE-luc reporters. 17 beta -Estradiol failed to activate ER beta -AP-1 responses while activating ER alpha -AP-1, ER alpha -ERE, ER beta -ERE mediated transcription. On the other hand, antiestrogens such as tamoxifen enhanced AP-1 mediated transactivation through both ER a lpha and ER beta. An ER alpha positive human breast cancel cell line, MCF-7 , also showed the same manner of AP-1 mediated transactivation through ER a lpha. When NIH 3T3 with ER alpha and MCF-7 were co-transfected with ER beta , E-2 dependent AP-1 responses decreased in both cell lines depending on th e amount of the ERP expression plasmid, These results suggest that ER alpha and ER beta may function in opposition with ER beta actually suppressing t he function of ER alpha in AP-1 mediated transactivation. (C) 2001 Elsevier Science Ltd. All rights reserved.