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

基本信息

批准号：
7908146
负责人：
Hong Chen
金额：
$ 3.91万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7908146
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

项目摘要

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）：结肠癌是美国最常见的癌症之一。不良的预后也使其成为最致命的癌症之一。饮食因素与结肠癌的肿瘤发生和发育密切相关。大豆食品和大豆生物活性成分与消耗大量大豆食品的种群中的结肠癌发病率降低有关。但是，存在争议和机制，大豆产物和大豆生物活性成分发挥抗癌作用仍然未知。由于缺乏关于大豆食品预防潜力机制的科学证据，因此没有对美国人提出营养建议。基于当前对结肠癌的知识和有关大豆食品有益作用的初步数据，本提案将检验以下假设：饮食大豆通过在Wnt信号途径的特定基因上通过表观遗传学编程调节结肠癌的发展。早期的孕产妇暴露模型将用于后代大鼠结肠大豆食品的表观遗传编程。使用包括对CpG岛的甲基化分析和染色质免疫沉淀结合到途径特异性微阵列的技术，该提案中的特定目的包括：1）沿Wnt信号传导途径识别特定基因，这些基因通过母体大豆饮食在表观上进行了改性的特定基因； 2）确定大豆食品在大鼠中在大鼠中影响Wnt途径的程度； 3）监测后代大鼠的后代大鼠的后代终生生结肠癌的保护。该项目的发现将提高我们对表观遗传水平大豆产品抗癌机制的理解，并促进未来的实验设计，以进一步研究大豆食品和结肠癌预防。公共卫生相关性：该项目的发现将提高我们对表观遗传水平大豆产品抗癌机制的理解，并帮助未来的实验设计，以进一步研究大豆食品和结肠癌预防。获得的数据将在未来促进转化研究，以定义针对美国人群的大豆食品的饮食建议。