Notch Signaling in Mammary Development and Tumorigenesis

描述(申请人提供)：Noch信号定义了一种进化上保守的细胞相互作用机制，该机制广泛控制后生动物中细胞命运的获得，从而深刻地影响细胞的分化、凋亡和增殖。在人类中，Notch信号的异常与多种致病条件有关，其在肿瘤发生中的作用日益受到重视，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，这些模型和试剂现在使我们能够在细胞水平上系统地解决Notch信号整合的基本问题，特别是它如何与Notch信号与其他细胞元件的协同作用影响、引起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.