Differential effect of estradiol and bisphenol A on Set8 and Sirt1 expression in prostate cancer

Exposure to estrogenic compounds has been shown to epigenetically reprogram the prostate and may contribute to prostate cancer. The goal of this study was to determine the effect of physiological doses of estradiol and bisphenol A (BPA) on the expression of histone modifying enzymes (HMEs) in prostate cancer. Using two human prostate cancer cell lines we examined the expression of Set8, a histone methyltransferase, and Sirt1, a histone deacetylase, after exposure to estrogen or BPA. These experiments were carried out in the presence of natural hormones to understand the impact of additional exposure to estrogen or BPA on HME expression. We found differential expression of the HMEs in the different models and between the different compounds. Further, we determined that the changes in gene expression occurred via estrogen receptor signaling using the ER antagonist, ICI 182,780 (fulvestrant). Interestingly we found that the combination of ICI with estrogen or BPA greatly affected the expression of Set8, even when the hormone alone had no effect. This study demonstrates that the effects of estrogen and BPA on HME expression vary and that the presence of both the estrogen receptor and androgen receptor may be important for therapeutic intervention.