Reversal of Estrogen Receptor Beta Epigenetic Gene Silencing in Prostatic Adenocarcinoma by Soy Protein-Derived Isoflavonoid Supplementation
Annual summary rept. 19 Mar 2008-18 May 2009
WAKE FOREST UNIV WINSTON-SALEM NC SCHOOL OF HEALTH SCIENCES
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The purpose of this study was to evaluate the effect of a 4-week soy isoflavonoid treatment at a dose of 100mgday on DNA promoter methylation density of the estrogen receptor beta ER beta gene in men with organ localized prostate cancer. We hypothesized that ER epigenetic silencing through DNA promoter methylation in neoplastic prostatic epithelial cells can be reversed by dietary soy isoflavonoids when given at physiologically achievable levels, as shown by a positive correlation between serum andor intraprostatic isoflavonoid concentrations and ER beta expression and an inverse correlation with neoplastic cell proliferation. A 4-week treatment with soy isoflavonoids did not result in a decrease in ER beta DNA promoter methylation within the prostate tissue. ER beta protein expression did not differ when analyzed by treatment group in prostatic adenocarcinoma, normal prostate tissue, or BPH. Isoflavonoid concentrations within the prostate tissue did not concentrate above serum levels in the soy isoflavonoid treatment group. ER beta DNA promoter methylation in prostatic adenocarcinoma was increased in the soy treatment group when compared to the placebo protein treatment group P0.02. A concomitant decrease in ER beta protein expression was seen in the neoplastic prostate P0.06 epithelium. Short-term soy isoflavonoid at 100mgday did not alter estrogen receptor beta DNA promoter methylation but increased ER beta DNA promoter methylation in the neoplastic prostate tissue.
- Medicine and Medical Research