Elucidating the role of new RasGAP tumor suppressors in cancer

描述（由申请人提供）：Ras通路是人类癌症中最常见的不受管制的通路之一。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不存在，尽管该通路被过度激活。我们已经确定了两个RasGAP基因，它们似乎在乳腺癌中起肿瘤抑制作用。该应用程序的目标是：1)了解这些蛋白的功能和相互作用；2)阐明这些基因独立或协同调节乳腺癌发展、进展和/或耐药性的机制；3)确定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子集进展的基础，将阐明Ras信号的新方面，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.