Notch Signaling in Mammary Development and Tumorigenesis

描述（由申请人提供）：Notch信号传导定义了一种进化上保守的细胞相互作用机制，其广泛控制后生动物中的细胞命运获得，并因此深刻影响细胞分化、凋亡和增殖。在人类中，Notch信号传导异常与多种致病性疾病有关，并且其在癌症发生中的参与越来越受到重视，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，这些模型和试剂现在使我们能够系统地解决Notch信号在细胞水平整合的基本问题，特别是，它如何与Notch信号与其他细胞因子的协同作用相关，以影响，引起或维持乳腺上皮中的肿瘤发生。公共卫生相关性：我们的工作直接解决了Notch信号传导与乳腺肿瘤发生之间的联系。我们正在利用我们产生的新型转基因小鼠来研究Notch信号在乳腺上皮中的作用，同时我们还使用果蝇遗传学作为一种强大的工具来研究Notch信号如何将其作用与其他细胞因子整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，从而了解其在乳腺癌中的作用。

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.