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.