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Requirement for Rac1 in a K-ras–Induced Lung Cancer in the Mouse

2007; American Association for Cancer Research; Volume: 67; Issue: 17 Linguagem: Inglês

10.1158/0008-5472.can-07-2300

1538-7445

Joseph L. Kissil, Marita J. Walmsley, Linda Hanlon, Kevin M. Haigis, Carla F. Bender Kim, E. Alejandro Sweet‐Cordero, Matthew S. Eckman, David A. Tuveson, Anthony J. Capobianco, Victor L. J. Tybulewicz, Tyler Jacks,

Cell death mechanisms and regulation

Abstract Given the prevalence of Ras mutations in human cancer, it is critical to understand the effector pathways downstream of oncogenic Ras leading to transformation. To directly assess the requirement for Rac1 in K-ras–induced tumorigenesis, we employed a model of lung cancer in which an oncogenic allele of K-ras could be activated by Cre-mediated recombination in the presence or absence of conditional deletion of Rac1. We show that Rac1 function is required for tumorigenesis in this model. Furthermore, although Rac1 deletion alone was compatible with cell viability and proliferation, when combined with K-ras activation in primary epithelial cells, loss of Rac1 caused a profound reduction in proliferation. These data show a specific requirement for Rac1 function in cells expressing oncogenic K-ras. [Cancer Res 2007;67(17):8089–94]