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 elements (EREs). Investigations of AP-1 mediated transactivation through ER have been performed with rather complex promoters such as insulin like growth factor 1 (IGF-1) and collagenase promoters. In the present study, we investigated AP-1 mediated transactivation through ERalpha and ERbeta with a less complicated reporter consisting of only consensus AP-1 motifs. NIH 3T3 cells were transiently transfected with human ERalpha and ERbeta expression plasmids and AP-1-luc and ERE-luc reporters. 17beta-Estradiol failed to activate ERbeta-AP-1 responses while activating ERalpha-AP-1, ERalpha-ERE, ERbeta-ERE mediated transcription. On the other hand, antiestrogens such as tamoxifen enhanced AP-1 mediated transactivation through both ERalpha and ERbeta. An ERalpha positive human breast cancel cell line, MCF-7, also showed the same manner of AP-1 mediated transactivation through ERalpha. When NIH 3T3 with ERalpha and MCF-7 were co-transfected with ERbeta, E2 dependent AP-1 responses decreased in both cell lines depending on the amount of the ERbeta expression plasmid. These results suggest that ERalpha and ERbeta may function in opposition with ERbeta actually suppressing the function of ERalpha in AP-1 mediated transactivation.
Maruyama
S
S
Department of Cancer Research, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, 1-2-3 Kasumi, Minami-ku, 734-8553, Hiroshima, Japan.
Fujimoto
N
N
Asano
K
K
Ito
A
A
D016475:3T3 Cells; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000378:metabolism*; D020218:Response Elements; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; D018808:Transcription Factor AP-1; D004958:Estradiol