Analysis of the promoter-specific estrogenic potency of the phytoestrogens genistein, daidzein and coumestrol.
Estrogens modulate the transcription of sensitive genes either via binding of the activated ER to responsive elements in their promoter region or via binding of the activated ER to transcription factors like NFkappaB. In this study we have analyzed the effects of the phytoestrogens daidzein, coumestrol and genistein in promoter-specific reporter gene systems. The dose-dependent ability to stimulate an ERE-bearing reporter in MVLN breast cancer cells was compared to the dose-dependent ability to repress the IL-1beta-stimulated reporter in U2OS osteosarcoma cells. Coumestrol, daidzein and genistein stimulate the expression of the ERE-dependent reporter in MVLN cells and repress the activity of the IL-6 promoter in U2OS cells in a dose-dependent manner. Interestingly, the relative potency of all phytoestrogens to repress the activity of the IL-6 promoter in U2OS cells was much higher than their potency to stimulate the ERE-dependent reporter in MVLN cells. We assume that the demonstrated promoter-specific potency therefore could be an important mechanism to explain a tissue-specific action of some of these compounds.
Zierau
Oliver
O
Institute for Zoology, Technische Universität Dresden, Zellescher Weg 20, 02127 Dresden, Germany. Oliver.Zierau@mailbox.tu-dresden.de
Kolba
Susanne
S
Olff
Sabine
S
Vollmer
Günter
G
Diel
Patrick
P
D045744:Cell Line, Tumor; D003375:Coumestrol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D048789:Phytoestrogens / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects
D007529:Isoflavones; D048789:Phytoestrogens; C004742:daidzein; D019833:Genistein; D003375:Coumestrol