Requirement for Rac1 in a K-ras-induced lung cancer in the mouse

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

Research output: Contribution to journalArticle

125 Citations (Scopus)

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 languageEnglish
Pages (from-to)8089-8094
Number of pages6
JournalCancer Research
Volume67
Issue number17
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

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Lung Neoplasms
Carcinogenesis
Genetic Recombination
Cell Survival
Epithelial Cells
Alleles
Cell Proliferation
Mutation
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kissil, J. L., Walmsley, M. J., Hanlon, L., Haigis, K. M., Kim, C. F. B., Sweet-Cordero, A., ... Jacks, T. (2007). Requirement for Rac1 in a K-ras-induced lung cancer in the mouse. Cancer Research, 67(17), 8089-8094. https://doi.org/10.1158/0008-5472.CAN-07-2300

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 journalArticle

Kissil, JL, Walmsley, MJ, Hanlon, L, Haigis, KM, Kim, CFB, Sweet-Cordero, A, Eckman, MS, Tuveson, DA, Capobianco, AJ, Tybulewicz, VLJ & Jacks, T 2007, 'Requirement for Rac1 in a K-ras-induced lung cancer in the mouse', Cancer Research, vol. 67, no. 17, pp. 8089-8094. https://doi.org/10.1158/0008-5472.CAN-07-2300
Kissil JL, Walmsley MJ, Hanlon L, Haigis KM, Kim CFB, Sweet-Cordero A et al. Requirement for Rac1 in a K-ras-induced lung cancer in the mouse. Cancer Research. 2007 Sep 1;67(17):8089-8094. https://doi.org/10.1158/0008-5472.CAN-07-2300
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. / Requirement for Rac1 in a K-ras-induced lung cancer in the mouse. In: Cancer Research. 2007 ; Vol. 67, No. 17. pp. 8089-8094.
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