MOLECULAR EFFECTS OF GENISTEIN ON ESTROGEN-RECEPTOR MEDIATED PATHWAYS

Genistein, a component of soy products, may play a role in the prevent ion of breast and prostate cancer, However, little is known about the molecular mechanisms involved, In the present study, we examined the e ffects of genistein on the estrogen receptor positive human breast can cer cell line MCF-7. We observed that genistein stimulated estrogen-re sponsive pS2 mRNA expression at concentrations as low as 10(-8) M and these effects can be inhibited by tamoxifen, We also showed that genis tein competed with [H-3]estradiol binding to the estrogen receptor wit h 50% inhibition at 5 x 10(-7) M. Thus, the estrogenic effect of genis tein would appear to be a result of an interaction with the estrogen r eceptor, The effect of genistein on growth of MCF-7 cells was also exa mined, Genistein produced a concentration-dependent effect on the grow th of MCF-7 cells, At lower concentrations (10(-8)-10(-6) M) genistein stimulated growth, but at higher concentrations (>10(-5) M) genistein inhibited growth. The effects of genistein on growth at lower concent rations appeared to be via the estrogen receptor pathway, while the ef fects at higher concentrations were independent of the estrogen recept or, We also found that genistein, though estrogenic, can interfere wit h the effects of estradiol, In addition, prolonged exposure to geniste in resulted in a decrease in estrogen receptor mRNA level as well as a decreased response to stimulation by estradiol.