Notch Signaling in Mammary Development and Tumorigenesis

描述（由申请人提供）：Notch信号定义了一种进化上保守的细胞相互作用机制，广泛控制后生动物细胞命运获取，从而深刻影响细胞分化、凋亡和增殖。在人类中，Notch信号异常与多种致病性疾病有关，其在癌变中的作用越来越受到重视，因此Notch已成为癌症治疗的重要潜在靶点。我们建议探索我们开发的特定模型和独特的转基因试剂，现在使我们能够系统地解决细胞水平上Notch信号整合的基本问题，特别是Notch信号与其他细胞元件的协同作用如何影响、导致或维持乳腺上皮的肿瘤发生。

DESCRIPTION (provided by applicant): Notch signaling defines an evolutionarily conserved cell interaction mechanism that broadly controls cell fate acquisition in metazoans and consequently, profoundly affects cellular differentiation, apoptosis and proliferation. In humans, Notch signaling abnormalities have been linked to a variety of pathogenic conditions and its involvement in carcinogenesis is being increasingly appreciated, thus Notch has become an important potential target for cancer therapy. We propose to explore specific models and unique transgenic reagents we developed which now allow us to address systematically the fundamental question of Notch signal integration at the cellular level, and in particular, how it relates to the synergy of Notch signals with other cellular elements to influence, cause or sustain oncogenesis in the mammary epithelium.