TY - JOUR
T1 - Requirement for Rac1 in a K-ras-induced lung cancer in the mouse
AU - Kissil, Joseph L.
AU - Walmsley, Marita J.
AU - Hanlon, Linda
AU - Haigis, Kevin M.
AU - Kim, Carla F.Bender
AU - Sweet-Cordero, Alejandro
AU - Eckman, Matthew S.
AU - Tuveson, David A.
AU - Capobianco, Anthony J.
AU - Tybulewicz, Victor L.J.
AU - Jacks, Tyler
PY - 2007/9/1
Y1 - 2007/9/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-07-2300
DO - 10.1158/0008-5472.CAN-07-2300
M3 - Article
C2 - 17804720
AN - SCOPUS:34548583283
VL - 67
SP - 8089
EP - 8094
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 17
ER -