Selenium Isoflavones and Prostate Cancer Risk Reduction

描述（由申请人提供）：本领域申请中描述的研究响应前列腺癌进展审查小组（PRG）报告中的建议。最近的数据表明，高硒（Se）的摄入或状态提供了对前列腺癌的保护作用。PRG报告建议“支持旨在更好地了解……前列腺生理学的营养物质如……硒”。本工作的目的是解释硒和异黄酮在前列腺癌保护作用的生化和分子机制。具体目的1是证明硒和异黄酮的饮食摄入量的差异，单独或不同组合，将改变Noble大鼠前列腺雌激素代谢和雌激素调节基因的表达。电泳迁移位移测定将测量雌激素：ER复合物与其DNA反应元件的结合。连续转录分析将量化这种结合对内质网调控基因转录率的影响。RT-PCR分析将测量相同基因的mRNA稳态水平。特异性目的2是利用抑制减法杂交和阵列筛选技术，鉴定Noble大鼠前列腺背外侧表达随硒和异黄酮摄入量差异而变化的其他基因。这项工作将完成PRG和NIH五年计划“前列腺癌规划”概述的目标，包括1)“确定特定饮食因素在癌症病因和预防中的作用”；加深对……中的角色的理解。《前列腺生理营养》；3)“这些营养素改变风险的机制”的定义；4)“营养物质对前列腺分子事件的影响”的论证。根据美国国立卫生研究院的报告，“食物成分对前列腺分子事件的影响尚不清楚”。硒和异黄酮调控基因的发现将“确定关键膳食成分消耗的生物标志物，特别是微量和大量营养素”。

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".