Maternal-Fetal Nutrition Controls Expression of Cell Cycle Genes in Offspring

描述（由申请人提供）： 母体营养补充或暴露于环境因素可能会改变乳腺的代谢过程和伴随的表观基因组改变，从而使乳腺在以后的生活中易患癌症。母亲的低蛋白饮食与许多成人疾病的风险有关，包括致癌物诱发的乳腺肿瘤。然而，母亲低蛋白饮食与乳腺癌发病风险之间的机制尚不清楚，这阻碍了我们进一步确定母亲营养在预防乳腺癌中的生理作用。肿瘤基因，特别是抑癌基因在肿瘤发生发展过程中的转录调控受表观遗传机制的控制，这使其成为一个重要的研究领域。我们的贡献在于阐明母体低蛋白饮食参与调节p21（一个潜在的乳腺肿瘤抑制基因）的具体机制。拟议的研究不仅将阐明这些表观遗传因子参与细胞周期基因表达及其调控的具体机制，还将为临床干预和治疗提供新的途径。随着我们对基因表达的表观遗传控制的理解不断扩大，针对这一水平的基因调控的新的治疗方法无疑将出现。本项目的研究结果将有助于我们从表观遗传学水平上理解母亲饮食控制的机制，并为进一步研究食物和乳腺癌预防奠定基础。

DESCRIPTION (provided by applicant): Maternal nutrient supplementation or exposure to environmental agents may change metabolic processes in mammary gland and the accompanied alteration in epigenome thereby predisposing mammary gland to the development of cancers later in life. Maternal low protein diet has been associated with the risk of a number of adult diseases, including developing carcinogen-induced mammary tumor. However mechanistic basis of the relationship between maternal low protein diet and subsequent mammary gland cancer risk is unclear, which retards our further determining the physiological role of maternal nutrition in cancer prevention. Transcriptional regulation of cancer genes, particularly tumor suppressor genes, during cancer development is governed by epigenetic mechanisms, which makes it an important area of investigation. Our contribution here is to clarify the specific mechanism(s) by which maternal low protein diet participates in regulation of p21, a potential breast tumor suppressor gene. The proposed studies will not only clarify the specific mechanism(s) by which these epigenetic factors participate in a cell cycle gene expression and its regulation, but also provide valuable insight into new avenues for clinical intervention and treatment. As our understanding of epigenetic control of gene expression continues to expand, novel therapeutic approaches targeting this level of gene regulation will undoubtedly emerge. Findings from this project will improve our understandings on mechanisms of maternal dietary control at epigenetic level and lay the foundation for further research on foods and breast cancer prevention.