REGULATION OF MAMMARY CANCER BY HORMONES

我们的总体目标是确定荷尔蒙和生长因子的作用 在不同表型和癌基因激活的调控中 小鼠乳腺癌变。 在美国，每九名女性中就有一名可能在 她的一生。女性乳腺癌的病因尚未确定。 流行病学研究表明，荷尔蒙对 乳房的生长和分化以及乳房的发育 乳腺癌。荷尔蒙相关因素，如月经初潮早、晚 更年期，早年足月妊娠，与 增加或降低患乳腺癌的风险。乳腺癌是 以形态、核型、转移的异质性为特征 能力、荷尔蒙独立性或荷尔蒙依赖性和对 心理治疗。综合起来，这些特征提供了间接证据 乳腺癌必须通过多种途径进展的证据。这个 参与调控这些癌症通路的因素尚未被 已定义。 我们已经开发了一个明确的培养系统，在这个系统中，特定的激素 目前接触致癌物的时间左右会影响发病率和 乳腺转化子的类型以及 与乳腺癌的发生有关。我们的工作假设是 癌变的启动受有丝分裂环境的调节。 大约在接受致癌物治疗的时候。我们建议研究一下 激素和生长因子在我们定义的培养系统中 乳腺表型和癌基因激活的调控 致癌。我们将研究激素和生长因子在 调节原癌基因的表达，DNA加合物的修复， 它们在转化子选择和激素相互作用中的作用 和生长因子在癌变中的作用。此外，我们还克隆了一本小说 转化基因，这可能是另一个分子探针 分析致癌过程中的序贯变化。广泛的分子和 将对该基因进行生物学表征。

Our overall goal is to determine the role of hormones and growth factors in the regulation of different phenotypes and oncogene activations in mouse mammary carcinogenesis. One out of nine women in the USA is likely to develop breast cancer during her lifetime. The etiology of breast cancer in women has not been defined. Epidemiological studies indicate that hormones are essential for the growth and differentiation of the breast as well as the development of breast cancer. Hormone related factors such as early age of menarche, late menopause, full term pregnancy at an early age, are associated with and increase or decrease in risk for breast cancer. Breast cancer is characterized as being heterogeneous in morphology, karyotypes, metastatic capabilities, hormone independence or hormone dependence and response to therapy. Taken together these characteristics provide circumstantial evidence that breast cancer must progress by a variety of pathways. The factors involved in the modulation of these cancer pathways have not been defined. We have developed a defined culture system in which the specific hormones present around the time of carcinogen exposure affect the incidence and type of mammary transformants as well as the molecular events that are associated with mammary carcinogenesis. Our working hypothesis is that the initiation of carcinogenesis is modulated by the mitogenic environment around the time of carcinogen treatment. We propose to study the role of hormones and growth factors in our defined culture system on the regulation of the phenotype and oncogene activation in mammary carcinogenesis. We will study the role of hormones and growth factors in regulating the expression of proto-oncogenes, the repair of DNA adducts, their role in selection of transformants, and the interaction of hormones and growth factors in carcinogenesis. Additionally we have cloned a novel transforming gene that is potentially another molecular probe for the analysis of sequential changes in carcinogenesis. Extensive molecular and biological characterization of the gene will be carried out.