Journal Article

Molecular effects of genistein on estrogen receptor mediated pathways

Thomas T.Y. Wang, Neeraja Sathyamoorthy and James M. Phang

in Carcinogenesis

Volume 17, issue 2, pages 271-275
Published in print February 1996 | ISSN: 0143-3334
Published online February 1996 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.2.271
Molecular effects of genistein on estrogen receptor mediated pathways

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Genistein, a component of soy products, may play a role in the prevention of breast and prostate cancer. However, little is known about the molecular mechanisms involved. In the present study, we examined the effects of genistein on the estrogen receptor positive human breast cancer cell line MCF-7. We observed that genistein stimulated estrogen-responsive pS2 mRNA expression at concentrations as low as 10−8 M and these effects can be inhibited by tamoxifen. We also showed that genistein competed with (3H)estradiol binding to the estrogen receptor with 50% inhibition at 5 × 10−7 M. Thus, the estrogenic effect of genistein would appear to be a result of an interaction with the estrogen receptor. The effect of genistein on growth of MCF-7 cells was also examined. Genistein produceda concentration-dependent effect on the growth of MCF-7 cells. At lower concentrations (10−8-10−6 M) genistein stimulated growth, but at higher concentrations (>10−5M) genistein inhibited growth. The effects of genistein on growth at lower concentrations appeared to be via the estrogen receptor pathway, while the effects at higher concentrations were independent of the estrogen receptor. We also found that genistein, thoughestrogenic, can interfere with the effects of estradiol. In addition, prolonged exposure to genistein resulted in a decrease in estrogen receptor mRNA level as well as a decreased response to stimulation by estradiol.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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