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。公共卫生相关性：我们的工作直接解决了Notch信号与乳腺肿瘤发生之间的联系。我们正在利用我们培育的新型转基因小鼠来研究Notch信号在乳腺上皮中的作用，同时我们还利用果蝇遗传学作为一个强大的工具来研究Notch信号如何将它们的作用与其他细胞元件结合起来影响细胞增殖。我们的目标是深入了解Notch信号在细胞增殖中的作用，从而了解它在乳腺癌中的作用。

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. PUBLIC HEALTH RELEVANCE: Our work directly addresses the link between Notch signaling and tumorigenesis in the mammary gland. We are taking advantage of novel transgenic mice we generated to study the effects of Notch signals in the mammary epithelium, while we also use Drosophila Genetics as a powerful tool to examine how Notch signals integrate their action with other cellular elements to affect cell proliferation. Our goal is to gain insights into the involvement of Notch signaling in cell proliferation and consequently its involvement in breast cancer.