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.
| Original language | English |
|---|---|
| Pages (from-to) | 8089-8094 |
| Number of pages | 6 |
| Journal | Cancer Research |
| Volume | 67 |
| Issue number | 17 |
| DOIs | |
| State | Published - Sep 1 2007 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Requirement for Rac1 in a K-ras-induced lung cancer in the mouse. / Kissil, Joseph L.; Walmsley, Marita J.; Hanlon, Linda; Haigis, Kevin M.; Kim, Carla F Bender; Sweet-Cordero, Alejandro; Eckman, Matthew S.; Tuveson, David A.; Capobianco, Anthony J; Tybulewicz, Victor L J; Jacks, Tyler.
In: Cancer Research, Vol. 67, No. 17, 01.09.2007, p. 8089-8094.Research output: Contribution to journal › Article
}
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.
UR - http://www.scopus.com/inward/record.url?scp=34548583283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548583283&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-2300
DO - 10.1158/0008-5472.CAN-07-2300
M3 - Article
VL - 67
SP - 8089
EP - 8094
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 17
ER -