Estrogen receptor activation and estrogen-regulated gene expression are unaffected by methylseleninic acid in LNCaP prostate cancer cells.

Prostate cancer is the most frequently diagnosed cancer and a leading cause of cancer deaths in American men. High dietary intake and status of the essential trace element selenium (Se) have been consistently correlated with reduced risk for prostate cancer. One molecular mechanism by which Se may reduce prostate cancer risk is by catalyzing disulfide bond formation or, otherwise, complexing with reactive sulfhydryl groups in transcription factors, thus altering their binding to DNA and regulation of gene expression. Estrogen plays a role in the etiology of prostate cancer. Estrogen receptors contain cysteines in zinc fingers that are susceptible to oxidation and internal disulfide bond formation, which can prevent DNA binding. We hypothesized that Se alteration of estrogen receptor (ER) binding to DNA and estrogen-regulated gene expression may be one mechanism by which it exerts its chemopreventive effects. LNCaP human prostate cancer cells were treated with 0.05 mumol/L (control) or 5.0 mumol/L (high) Se as methylseleninic acid (MSA). Electrophoretic mobility shift assays showed that binding of ER-beta to the estrogen response element was a nonsignificant 14% lower in cells treated with high MSA. Run-on transcription assays showed no significant changes in transcription rates for estrogen-regulated genes, and steady-state mRNA levels for those genes, assayed by reverse transcription-polymerase chair reaction, were likewise unaffected by MSA. These results suggest that the well-documented chemopreventive effects of Se against prostate cancer may be mediated by mechanisms other than inhibition by monomethylated Se compounds of ER-beta activation or estrogen-regulated gene expression.