Gene-Specific Epigenetic Programming of WNT Signaling Pathway by Dietary Soy

膳食大豆对 WNT 信号通路进行基因特异性表观遗传编程

• 批准号: 7640719
• 负责人: Hong Chen
• 金额: $ 7.42万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7640719
• 关键词: Aberrant crypt foci; Acetylation; Adult; Affect; Age; American; Azoxymethane; Classification; Colon; Colon Carcinoma; Colonic Neoplasms; Colorectal Cancer; Complex; Coupled; CpG Islands; Custom; DNA Methylation; DNA Microarray Chip; Data; Development; Diet; Diet Modification; Dietary Factors; Dose; Elderly; Epidemiology; Epigenetic Process; Epithelial; Epithelium; Experimental Designs; Exposure to; Funding Mechanisms; Future; Gene Expression; Gene Targeting; Genes; Genistein; Genus Cola; Histone H3; Hypermethylation; Incidence; Investigation; Knowledge; Lactation; Length; Life; Link; Living Wills; Malignant Neoplasms; Malignant neoplasm of prostate; Maternal Exposure; Methylation; Modeling; Modification; Monitor; Natural regeneration; Nutritional; Pathway interactions; Phytoestrogens; Play; Population; Pregnancy; Promoter Regions; Rattus; Recommendation; Research; Reverse Transcriptase Polymerase Chain Reaction; Role; Soy Foods; Techniques; Testing; Time; Translational Research; United States; WNT Signaling Pathway; Weaning; Work; base; cancer diagnosis; cancer prevention; chromatin immunoprecipitation; design; histone modification; improved; malignant breast neoplasm; offspring; outcome forecast; programs; promoter; public health relevance; research study; soy; tumorigenesis

DESCRIPTION (provided by applicant): Colon cancer is one of the most frequently diagnosed cancers in the United States. Poor prognosis also makes it one of the deadliest cancers. Dietary factors are closely associated with tumorigenesis and development of colon cancer. Soy foods and soy bioactive components have been linked to lower colon cancer incidence in populations consuming large quantity of soy foods. However there are controversies and mechanisms by which soy products and soy bioactive components exert anticancer effects remain unknown. Because of lack of scientific evidence on the mechanisms of soy foods' cancer prevention potentials, there are no nutritional recommendations made to Americans. Based on current knowledge of colon cancer and preliminary data on beneficial actions of soy foods, the present proposal will test the hypothesis that dietary soy modulates colon cancer development through epigenetic programming at specific genes of WNT signaling pathway. An early maternal exposure model will be used for epigenetic programming by soy foods in colon of offspring rats. Using techniques including methylation analysis of CpG islands and chromatin immunoprecipitation coupled to a pathway-specific microarray, specific aims in this proposal include: 1) to identify specific genes along the WNT signaling pathway that are modified epigenetically by maternal soy diets; 2) to determine the extent to which the WNT pathway is affected in colon in rats by soy foods; and 3) to monitor protection from getting colon cancer in later life of offspring rats with life long exposure to soy foods. Findings from this project will improve our understandings on anticancer mechanisms of soy products at epigenetic level and facilitate future experimental design for further research on soy foods and colon cancer prevention. PUBLIC HEALTH RELEVANCE: Findings from this project will improve our understandings on anticancer mechanisms of soy products at epigenetic level and aid future experimental design for further research on soy foods and colon cancer prevention. Data obtained will facilitate translational research in the future to define dietary recommendations for soy foods for American populations.

描述（由申请人提供）：结肠癌是美国最常诊断的癌症之一。预后不良也使其成为最致命的癌症之一。饮食因素与结肠癌的发生、发展密切相关。大豆食品和大豆生物活性成分与食用大量大豆食品的人群中结肠癌发病率降低有关。然而，大豆制品和大豆生物活性成分发挥抗癌作用的机制仍不清楚，存在争议。由于缺乏关于大豆食品预防癌症潜力机制的科学证据，没有向美国人提出营养建议。基于目前对结肠癌的认识和大豆食品有益作用的初步数据，本提案将验证膳食大豆通过WNT信号通路特定基因的表观遗传编程调节结肠癌发展的假设。早期母体暴露模型将用于后代大鼠结肠中大豆食物的表观遗传编程。使用包括CpG岛甲基化分析和染色质免疫沉淀与途径特异性微阵列偶联在内的技术，该提案的具体目标包括：1）鉴定沿着WNT信号通路被母体大豆饮食表观遗传修饰的特定基因; 2）确定大豆食品对大鼠结肠中WNT途径的影响程度;和3）监测终身暴露于大豆食品的后代大鼠在以后的生活中免受结肠癌的保护。本研究的发现将有助于我们在表观遗传学水平上对大豆制品的抗癌机制的理解，并为大豆食品和结肠癌预防的进一步研究提供实验设计。公共卫生相关性：本研究的发现将有助于我们在表观遗传学水平上对大豆制品的抗癌机制的理解，并为大豆食品和结肠癌预防的进一步研究提供实验设计。所获得的数据将促进未来的转化研究，以确定美国人口的大豆食品的饮食建议。