Influences of neonatal environment on mammary gland development in female balb/c mice

新生环境对雌性balb/c小鼠乳腺发育的影响

• 批准号: 288318-2006
• 负责人: Kerr, Leslie
• 金额: $ 1.75万
• 依托单位: Trent University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=395794
• 关键词: Influences; neonatal; environment; mammary; gland

Objectives:  To understand how early life experiences influence normal and malignant mammary gland development Hypothesis:  It is hypothesized that early life events will differentially influence hormone levels (e.g. glucocorticoids and estrogen), altering breast development as measured by alterations in protein and gene expression patterns (e.g. estrogen receptor (ER), glucocorticoid receptor (GR), p53) and related gland morphology (measured by alterations in TEB or lobulo-alveolar numbers and branching patterns).  The interactions between environment, protein and gene expression and related mammary gland development may predispose the breast to increased risk of cancer development later in life. Scientific Approach:   The proposed studies will add to the limited data on how early social environment impacts on mammary gland development and future cancer risk.  Neonatal handling (H) and maternal separation (MS), two well established animal models of early-life environmental manipulations, differentially influence the development and life-time activity of several systems including the CNS, immune and neuroendocrine.  Because the mammary gland is one of a few organ systems that completes its development postnatally, it may be uniquely susceptible to genetic and epigenetic modifications caused by physiological alterations due to neonatal experiences. These studies are unique in that they are the first to systematically examine the influences of prepubertal experiences on mammary gland development, which in turn possibly directs the accumulation of mutagenic events, increasing breast cancer risk. A better understanding of the significant influence that the early social environment has on breast development, including alterations of breast cancer susceptibility genes, will improve our prospects for breast cancer prevention.

目的：了解早期生活经历如何影响正常和恶性乳腺发育假设：据推测，早期生活事件将不同程度地影响激素水平（如糖皮质激素和雌激素），改变乳腺发育，如蛋白质和基因表达模式的改变所测量的（例如雌激素受体（ER）、糖皮质激素受体（GR）、p53）和相关腺体形态（通过TEB或小叶肺泡数量和分支模式的改变来测量）。环境，蛋白质和基因表达以及相关的乳腺发育可能使乳腺在以后的生活中患癌症的风险增加。科学方法： 拟议的研究将增加关于早期社会环境如何影响乳腺发育和未来癌症风险的有限数据。新生儿处理（H）和母体分离（MS）是两种建立良好的早期环境操作动物模型，对包括CNS在内的几个系统的发育和终生活动产生不同的影响，因为乳腺是在出生后完成其发育的少数器官系统之一，所以它可能对由新生儿经历引起的生理改变引起的遗传和表观遗传修饰特别敏感。这些研究的独特之处在于，它们是第一个系统地研究青春期前经历对乳腺发育的影响的研究，而乳腺发育反过来又可能指导诱变事件的积累，增加乳腺癌的风险。更好地了解早期社会环境对乳腺发育的重要影响，包括乳腺癌易感基因的改变，将改善我们预防乳腺癌的前景。