Selenium Isoflavones and Prostate Cancer Risk Reduction

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DESCRIPTION (provided by applicant): The research described in this AREA application is responsive to recommendations in the Report of the Prostate Cancer Progress Review Group (PRG). Recent data demonstrate that high selenium (Se) intake or status provides a protective effect against prostate cancer. The PRG report recommends "Support studies aimed at better understanding of the roles in...prostate physiology of nutrients such as ,,, selenium". The objective of this work is to explain biochemical and molecular mechanisms for the cancer protective effects of Se and isofiavones in prostate. Specific Aim 1 is to demonstrate that differences in dietary intake of Se and isoflavones, alone and in varying combinations, will alter estrogen metabolism and the expression of estrogen-regulated genes in Noble rat prostate. Electrophoretic mobility shift assays will measure binding of the estrogen:ER complex to its DNA response element. Run-on transcription assays will quantitate the effects of that binding on transcription rates for ER-regulated genes. RT-PCR analysis will measure steady state levels of mRNA for the same genes. Specific Aim 2 is to identify additional genes whose expression in Noble rat dorsolateral prostate varies with differences in Se and isoflavone intake, using suppression subtractive hybridization and array screening. This work will accomplish the objectives outlined by the PRG and by the NIH Five Year Plan "Planning for Prostate Cancer", including 1) "defining the role of specific dietary factors in the etiology and prevention of...cancer"; 2) increasing "understanding of the roles in...prostate physiology of nutrients"; 3) definition of "the mechanisms by which these nutrients alter risk"; and 4) demonstration of "the effects of nutrients on molecular events in the prostate". According to the NIH report "the effect of food constituents on molecular events in the prostate is unknown". Discovery of Se- and isoflavone-regulated genes will "identify biomarkers of the consumption of key dietary components, particularly micro- and macronutrients".