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. 2000 Oct 12;19(43):4970-8.
doi: 10.1038/sj.onc.1203828.

Estrogen receptor beta acts as a dominant regulator of estrogen signaling

K Pettersson  1 , F Delaunay, J A Gustafsson
Affiliations

Estrogen receptor beta acts as a dominant regulator of estrogen signaling

K Pettersson et al. Oncogene. .

Abstract

The physiological effects of estrogens are mediated by two intracellular transcription factors, the estrogen receptors (ERs), that regulate transcription of _target genes through binding to specific DNA _target sequences. Here we describe alterations in cellular responses to different ER agonists and to the anti-estrogenic compound tamoxifen resulting from co-expression of the two ERs in transient co-transfection experiments. Our results demonstrate that ERbeta can act as a negative or positive dominant regulator of ER activity. This is manifested through reduced transcriptional activity at low concentrations of estradiol (E2); increased antagonistic effects of tamoxifen on E2 stimulated activity; and enhanced agonistic action of the phytoestrogenic compound genistein. Furthermore, using chimeric proteins lacking the N-terminal activation function 1 (AF-1), we show that the differential responses of ERalpha and ERbeta to different agonists and antagonists are primarily dictated by inherent differences in the C-terminal ligand-binding domains of the receptors, whereas the magnitude of transcriptional activity is influenced by ERalpha AF-1, but not ERbeta AF-1. The ERalpha AF-1 activity appears to be modulated upon co-expression of both ERs. The alterations in transcriptional activity resulting from co-expression of ERalpha and ERbeta are probably due to the formation of alpha/beta heterodimeric complexes. This study demonstrates that co-localization and subsequent heterodimerization of ERalpha and ERbeta may result in receptor activity distinct from that of ER homodimers.

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