Molecular effects of genistein on estrogen receptor mediated pathways

Genistein, a component of soy products, may play a role in theprevention of breast and prostate cancer. However, little isknown about the molecular mechanisms involved. In the presentstudy, we examined the effects of genistein on the estrogenreceptor positive human breast cancer cell line MCF-7. We observedthat genistein stimulated estrogen-responsive pS2 mRNA expressionat concentrations as low as 10^–8 M and these effects canbe inhibited by tamoxifen. We also showed that genistein competedwith (³H)estradiol binding to the estrogen receptor with 50%inhibition at 5 x 10^–7 M. Thus, the estrogenic effectof genistein would appear to be a result of an interaction withthe estrogen receptor. The effect of genistein on growth ofMCF-7 cells was also examined. Genistein produceda concentration-dependenteffect on the growth of MCF-7 cells. At lower concentrations(10^–8-10^–6 M) genistein stimulated growth, but athigher concentrations (>10^–5M) genistein inhibitedgrowth. The effects of genistein on growth at lower concentrationsappeared to be via the estrogen receptor pathway, while theeffects at higher concentrations were independent of the estrogenreceptor. We also found that genistein, thoughestrogenic, caninterfere with the effects of estradiol. In addition, prolongedexposure to genistein resulted in a decrease in estrogen receptormRNA level as well as a decreased response to stimulation byestradiol.