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

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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.