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Prostate Specific Antigen Expression Is Down-Regulated by Selenium through Disruption of Androgen Receptor Signaling

¹Departments of Cancer Prevention and Population Sciences, ²Medicine, and ³Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York

A previous controlled intervention trial showed that selenium supplementation was effective in reducing the incidence of prostate cancer. Physiological concentrations of selenium have also been reported to inhibit the growth of human prostate cancer cells in vitro. The present study describes the observation that selenium was able to significantly down-regulate the expression of prostate-specific antigen (PSA) transcript and protein within hours in the androgen-responsive LNCaP cells. Decreases in androgen receptor (AR) transcript and protein followed a similar dose and time response pattern upon exposure to selenium. The reduction of AR and PSA expression by selenium occurred well before any significant change in cell number. With the use of a luciferase reporter construct linked to either the PSA promoter or the androgen responsive element, it was found that selenium inhibited the trans-activating activity of AR in cells transfected with the wild-type AR expression vector. Selenium also suppressed the binding of AR to the androgen responsive element site, as evidenced by electrophoretic mobility shift assay of the AR-androgen responsive element complex. In view of the fact that PSA is a well-accepted prognostic indicator of prostate cancer, an important implication of this study is that a selenium intervention strategy aimed at toning down the amplitude of androgen signaling could be helpful in controlling morbidity of this disease.

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