Selenium Isoflavones and Prostate Cancer Risk Reduction

硒异黄酮与降低前列腺癌风险

• 批准号: 6755471
• 负责人: MERRILL CHRISTENSEN
• 金额: $ 22.5万
• 依托单位: BRIGHAM YOUNG UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6755471
• 关键词: cancer risk; chemoprevention; dietary supplements; estrogen receptors; estrogens; gel mobility shift assay; gene expression; hormone metabolism; hormone regulation /control mechanism; laboratory rat; messenger RNA; nutrient intake activity; nutrition related tag; phytoestrogens; polymerase chain reaction; prostate; prostate neoplasms; receptor binding; selenium; subtraction hybridization

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".

描述（由申请人提供）：本 AREA 申请中描述的研究是对前列腺癌进展审查小组 (PRG) 报告中的建议的回应。最近的数据表明，高硒 (Se) 摄入量或状态可提供预防前列腺癌的保护作用。 PRG 报告建议“支持旨在更好地了解硒等营养素在前列腺生理学中的作用的研究”。这项工作的目的是解释硒和异黄酮在前列腺中的癌症保护作用的生化和分子机制。具体目标 1 是证明硒和异黄酮的膳食摄入量差异（单独或不同组合）将改变 Noble 大鼠前列腺中雌激素代谢和雌激素调节基因的表达。电泳迁移率变动分析将测量雌激素：ER 复合物与其 DNA 响应元件的结合。连续转录测定将定量该结合对 ER 调节基因转录率的影响。 RT-PCR 分析将测量相同基因的 mRNA 稳态水平。具体目标 2 是使用抑制消减杂交和阵列筛选来鉴定其他基因，这些基因在 Noble 大鼠背外侧前列腺中的表达随 Se 和异黄酮摄入量的差异而变化。这项工作将实现 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……癌症的病因学和预防中的作用”； 2) 增加“对营养素在……前列腺生理学中的作用的理解”； 3）“这些营养素改变风险的机制”的定义； 4) 演示“营养物质对前列腺分子事件的影响”。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”。硒和异黄酮调节基因的发现将“识别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”。

项目成果

Timing of supplementation of selenium and isoflavones determines prostate cancer risk factor reduction in rats.

• DOI: 10.1186/1743-7075-5-31
• 发表时间: 2008-11-10
• 期刊: NUTRITION & METABOLISM
• 影响因子: 4.5
• 作者: Tolman, Jessica R.;Lephart, Edwin D.;Setchell, Kenneth D. R.;Eggett, Dennis L.;Christensen, Merrill J.
• 通讯作者: Christensen, Merrill J.