Early Life Estrogenicity and Mammary Cancer Risk

生命早期雌激素和乳腺癌风险

• 批准号: 8180999
• 负责人: LEENA A. HILAKIVI-CLARKE
• 金额: $ 10.39万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-29 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8180999
• 关键词: Early; Life; Estrogenicity; Mammary; Cancer

Early Life Estrogenicity and Mammary Cancer Risk. While the timing of estrogen exposures has profound and often opposing effects on breast cancer suscepfibility, the molecular changes and programming that are altered by these exposures are almost entirely unknown. Dr. Hilakivi-Clarke and her team will focus on identifying key transcription factor-based signaling associated with increased mammary cancer risk in the mammary glands of rodents exposed to an elevated estrogenic environment in utero. We will determine the effects of these exposures on altering the sensitivity of the adult gland to E2, and on the endocrine responsiveness of mammary tumors arising in these glands. Data from these studies will be used to build computational models of ER-driven signaling associated with the effects of estrogens on increasing mammary gland susceptibility to neoplastic transformation and on endocrine responsiveness of mammary tumors. These data will also provide and unique powerful insights into the modeling in Projects 1 and 2.

早期生活雌激素和乳腺癌的风险。虽然雌激素暴露的时间 对乳腺癌的易变性、分子变化和 由这些曝光改变的编程几乎完全未知。希拉基维-克拉克博士和她 研究小组将专注于确定与乳腺癌发病率增加相关的关键转录因子信号。 啮齿类动物在子宫内暴露于升高的雌激素环境中的乳腺癌风险。我们将 确定这些暴露对改变成人腺体对E2的敏感性的影响，以及对 这些腺体中产生的乳腺肿瘤的内分泌反应。这些研究的数据将用于 建立ER驱动信号传导的计算模型，与雌激素对增加 乳腺癌易感性与乳腺内分泌反应性 肿瘤的这些数据还将为项目1和项目2中的建模提供独特而强大的见解。