Elucidating the role of new RasGAP tumor suppressors in cancer

描述（由申请人提供）：Ras途径是人类癌症中最常见的失调途径之一。RAS基因在广泛的肿瘤类型中发生突变;然而，RAS突变在乳腺癌中明显缺失，尽管该途径被过度激活。我们已经确定了两个RasGAP基因似乎在乳腺癌中起肿瘤抑制剂的作用。本申请的目的是1）了解这些蛋白质如何发挥功能和相互作用，2）阐明这些基因独立和协同调节乳腺癌发生、进展和/或耐药性的机制，3）建立这些基因在人类乳腺癌中失活的频率和临床环境。这项工作将作为理解为什么特定乳腺癌进展的一个子集的基础，将阐明Ras信号转导的新方面，并将揭示这些新的肿瘤抑制因子如何将Ras与其他信号网络联系起来。

DESCRIPTION (provided by applicant): The Ras pathway is one of the most commonly deregulated pathways in human cancer. RAS genes are mutated in a broad spectrum of tumor types; however, RAS mutations are conspicuously absent in breast cancer, despite the fact that the pathway is hyperactivated. We have identified two RasGAP genes that appear to function as tumor suppressors in breast cancer. The goal of this application is to 1) understand how these proteins function and interact, 2) elucidate the mechanism by which these genes independently and cooperatively regulate breast cancer development, progression, and/or drug resistance, and 3) establish the frequency and clinical setting in which these genes are inactivated in human breast cancer. This work will serve as a basis for understanding why a subset of specific breast cancers progress, will elucidate novel aspects of Ras signaling, and will reveal how these new tumor suppressors link Ras to other signaling networks.