MECHANISMS OF THE HORMONAL PREVENTION OF BREAST CANCER

乳腺癌是全世界最常见、最令人恐惧的女性癌症。 美国。乳腺癌的发病率增长缓慢，而且 在过去的20年里稳步增长。在大多数情况下的一致发现 流行病学研究表明，怀孕对母体的保护作用 人类乳腺癌的发病率。在动物模型中，提供的保护 通过短期接触低剂量的 雌激素和孕激素。细胞和分子水平的研究进展 激素的保护作用是一个关键问题，关系到 开发预防人类乳腺癌的方法。从长远来看 这个项目的目标是了解荷尔蒙是如何被使用的 自然而然地由有机体来阻止开发项目是为了 了解荷尔蒙是如何被生物体自然利用来防止 乳腺癌的发展。本计划中描述的方法 项目应用程序是独一无二的，因为它专注于Low的有限曝光 剂量的自然产生的荷尔蒙，以永久降低风险 乳腺癌的发展。该计划项目被设计为一个多- 纪律方法侧重于单一模式来解决问题 与预防人类乳腺癌直接相关。该模型是 激素(雌激素和孕激素)诱导的N-甲基-N-羟色胺的预防 亚硝脲诱发近交系Wistar-Furth雌鼠乳腺癌。 该方案项目由4个项目和3个核心设施组成。项目 1检查短期低剂量激素治疗的疗效， 抗性状态的持久性和组织定位。项目2 检测耐药状态下的细胞增殖动力学和 分析抗病状态所特有的核基质蛋白。项目 3检查易感和耐药状态的特定基因。 发育中的腺体及其特异性基因的表达和定位 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对致癌的作用 腺体的潜力。每个项目都依赖于实验 和智力贡献的动物资源核心和 显微镜与分子细胞化学核心。这个项目的成功之处 项目取决于个人提供的互补专业知识 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。这个 对乳腺细胞所涉及的基本生物学事件的理解 生长和激素诱导的分化将为 制定新的预防方法，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.