MECHANISMS OF THE HORMONAL PREVENTION OF BREAST CANCER

乳腺癌是女性最常见和最害怕的癌症， 美国的 乳腺癌的发病率缓慢上升， 在过去的20年里稳步增长。 在大多数情况下， 流行病学研究表明，怀孕对 人类乳腺癌的发病率。 在动物模型中， 短期暴露于低剂量的 雌激素和孕激素。 细胞和分子的理解， 激素的保护作用是一个关键问题， 开发人类乳腺癌的预防方法。 长期 这个项目的目标是了解激素是如何被使用的 自然由生物体，以防止发展项目是 了解激素是如何自然地被有机体用来防止 乳腺癌的发展。 本计划中所述的方法 项目应用程序是独特的，因为它侧重于低风险的有限暴露 剂量的天然激素，以永久降低风险， 乳腺癌的发展 该项目被设计为一个多- 学科方法侧重于解决一个问题的单一模式 与人类乳腺癌的预防直接相关。 该模型 激素（雌激素和孕激素）诱导的N-甲基-N- 亚硝基脲诱导的近交系Wistar-Furth雌性乳腺癌。 该计划项目包括4个项目和3个核心设施。 项目 1检查短期低剂量激素治疗的疗效， 持久性和耐药状态的组织定位。 计划2 检查了耐药状态下的细胞增殖动力学， 分析耐药状态特有的核基质蛋白。 项目 3研究了易感和抗性状态下特有的特定基因， 腺体的发育和特异性的表达定位 乳腺发育基因 项目4研究雌激素的重要性 孕激素受体的组成和功能 腺的潜力。 每个项目都依赖于实验 动物资源核心和 显微镜和分子细胞化学核心。 这项计划的成功 项目取决于个人提供的补充专业知识 肿瘤生物学，生殖生物学， 发育生物学、分子内分泌学和分子生物学。 的 了解乳腺细胞的基本生物学事件， 生长和生长诱导的分化将提供一个基本原理， 制定新的预防办法，以控制和扭转 人类乳腺癌的上升趋势。

Breast cancer is the most frequent and the most feared cancer in women in the United States. The incidence of breast cancer has increased slowly and steadily over the past 20 years. A consistent finding in most epidemiological studies has been the protective effect of pregnancy on the incidence of human breast cancer. In animal models the protection afforded by pregnancy can be mimicked by short-term exposure to low doses of estrogens and progestins. The cellular and molecular understanding of the protective effect of hormones is a critical question which is relevant to developing a prevention approach to human breast cancer. The long term goals of this program project are to understand how hormones are used naturally by the organism to prevent the development project are to understand how hormones are used naturally by th organism to prevent the development of breast cancer. The approach described in this Program Project application is unique as it focuses on a limited exposure of low doses of naturally-occurring hormones to permanently decrease the risk of breast cancer development. The Program Project is designed as a multi- disciplinary approach focused on a single model to address a question immediately relevant to prevention of human breast cancer. The model is the hormone (estrogen and progesterone)-induced prevention of N-methyl-N- nitrosourea - induced breast cancer in the inbred Wistar-Furth female at. The Program Project consists of 4 Projects and 3 Core facilities. Project 1 examines the efficacy of short-term low dose hormone treatments, the persistence and the tissue localization of the resistant state. Project 2 examines cell proliferation kinetics in the resistant state and the analysis of nuclear matrix proteins unique to the resistant state. Project 3 examines specific genes unique to the susceptible and resistant state ina the developing gland and the expression and localization of specific mammary developmental genes. Project 4 examines the importance of estrogen and progesterone receptor composition and function to the oncogenic potential of the gland. Each project is dependent upon the experimental and intellectual contributions of the Animal Resources Core and the Microscopy and Molecular Cytochemistry Core. The success of this Program Project depends on the complementary expertise provided by the individual investigators in the areas of tumor biology, reproductive biology, developmental biology, molecular endocrinology and molecular biology. The understanding of the fundamental biological events involved in mammary cell growth and hormone-induced differentiation will provide a rationale for developing new preventive approaches for controlling and reversing the rising tide of human breast cancer.