Estrogen receptor-dependent activation of AP-1 via non-genomic signalling

Linda Björnström¹ and Maria Sjöberg¹^,2

¹Dept. of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden

²Karo Bio AB, Novum, SE-141 57 Huddinge, Sweden

Nuclear Receptor 2004, 2:3doi:10.1186/1478-1336-2-3


Published:	14 June 2004

Abstract

Background

Ligand-bound estrogen receptor α (ERα) and estrogen receptor β (ERβ) modulate AP-1-dependent transcription via protein-protein interactions on DNA, in a manner that depends on the type of cells and the subtype of ER. We present here evidence for an additional mechanism by which ERs modulate the transcriptional activity of AP-1.

Results

We show that ERs located in the cytoplasm efficiently activate transcription at AP-1 sites in response to 17β-estradiol, while ERs present in the nucleus repress transcription under the same conditions. 17β-estradiol-induced activation of the coll-73-luc reporter correlated with cytoplasmic localization of various ERα and ERβ mutant receptors, and was inhibited in the presence of the full estrogen antagonist ICI 182,780 and the MAP-kinase inhibitor UO126. We also show that the selective estrogen receptor modulator (SERM) tamoxifen is as potent as 17β-estradiol in inducing activation of AP-1 when ERα is present in the cytoplasm.

Conclusions

These results suggest that non-genomic signalling is involved in the mechanism by which ERα and ERβ influence AP-1-dependent transcription. We have previously shown that Stat3 and Stat5 are targeted by non-genomic actions of ERs, and the results presented here allow us to conclude that ERs bound to 17β-estradiol mediate the transcriptional activation of promoters regulated by AP-1 and by Stat proteins via different combinations of signal transduction pathways. Our observations thereby provide new insights into the mechanisms by which ERs act at alternate response elements, and suggest a mechanism by which tamoxifen exerts its action as a tissue-selective agonist.