BIOLOGY OF NEOPLASTIC TRANSFORMATION IN BREAST CANCER

描述：首席调查员发现了一种小鼠乳腺肿瘤 用多瘤病毒构建转基因小鼠的模型 模仿肿瘤的中间T(MT)和相关位点特异性突变 乳腺癌从发病到转移的进展。PYV-Mt 转基因，它可以激活一些基因，但特别是它激活 磷脂酰肌醇-3-激酶(PI3-K)及其相关信号通路是一种 用于模拟人类的唯一合适的和生物相关的转基因 乳腺癌，自从c-erbB家族的酪氨酸激酶，它一直是 被证明激活PI3-K，已被认为与人类乳腺癌有关。这 提案侧重于确定这一模型的生物学的两个主要方面。 第一个是从选定的组织学中开发可移植的外生系。 肿瘤转化的阶段及其生物学潜力的特征 通过连续移植。二是对分子途径进行剖析。 参与了乳腺癌从良性向良性发展的过程 通过全面的基因表达谱分析转移。特别是，他们计划 为了检验PI3-K和/或下游信号中间产物的假设 是肿瘤转化、肿瘤发展的关键调节因子， 小鼠乳腺肿瘤模型中的转移。这个项目的目标是 开发一个特征明确的乳腺癌发展模型，并对其进行解剖 参与肿瘤形成的分子途径。

DESCRIPTION: The Principal Investigator has developed a mouse mammary tumor model derived from transgenic mice constructed with the polyoma virus (PyV) middle T (mT) and related site specific mutations, that mimic the neoplastic progression of breast carcinoma from its inception to metastasis. The PyV-mT transgene, which can activate a number of genes, but in particular it activates phosphatidylinositol - 3 - kinase (PI3-K) and its related pathways, is a uniquely appropriate and biologically relevant transgene for modeling human breast cancer, since the c-erbB family of tyrosine kinases, which have been shown to activate PI3-K, have been implicated in human breast cancer. This proposal focuses on two major aspects of determining the biology of this model. The first is to develop transplantable outgrowth lines from selected histologic stages of neoplastic transformation and characterize their biological potential by serial transplantation. The second is to dissect the molecular pathways involved in the progression of breast cancer from the benign state to the metastasis by comprehensive gene expression profiling. In particular, they plan to test the hypothesis that the PI3-K and/or downstream signaling intermediates are key regulators of neoplastic transformation, tumor development, and metastasis in the mouse mammary tumor model. The goal of this project is to develop a well-characterized model for breast cancer development and to dissect the molecular pathways involved in tumor formation.