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Biochem Biophys Res Commun. 1998 Dec 9;253(1):38-43.

Genistein-mediated attenuation of tamoxifen-induced antagonism from estrogen receptor-regulated genes.

Author information

  • 1Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA. jschwart@med.wayne.edu

Abstract

In this study we demonstrate that physiologic concentrations of genistein are sufficient to mediate agonism and to reverse the repressive effects of 4-hydroxytamoxifen on estrogen receptor (ER alpha)-responsive reporter genes. We also show that overexpression of the steroid receptor coactivator (SRC-1) potentiates transactivation by genistein-activated ER alpha and that coexpression of CBP (the cAMP response element binding protein coactivator) synergistically increases this signal. Exogenous expression of a nuclear receptor corepressor (NCoR) was, however, unable to alter genistein-mediated transactivation. In in vitro binding assays, we show that genistein, but not 4-hydroxytamoxifen, induces a direct interaction between radiolabeled ER alpha and a GST-SRC-1 fusion protein. More importantly, coincubation with genistein and 4-hydroxytamoxifen or genistein treatment following preincubation of the ER with 4-hydroxytamoxifen also resulted in a strong physical interaction with SRC-1. These findings imply that genistein-induced shifts in the coregulator status of ER alpha may be involved in transcriptional regulation and suggest that tamoxifen-mediated antagonism at ER-dependent genes is sensitive to attenuation by low levels of genistein.

PMID:
9875216
[PubMed - indexed for MEDLINE]
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