title: Requirement for Rac1 in a K-ras induced lung cancer in the mouse.
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.
authors.affiliation: Program in Molecular Oncogenesis, The Wistar Institute, Philadelphia, PA 19104, USA. jkissil@wistar.org
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kissil
authors.forename: Marita J
authors.initials: MJ
authors.lastname: Walmsley
authors.forename: Linda
authors.initials: L
authors.lastname: Hanlon
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Haigis
authors.forename: Carla F
authors.initials: CF
authors.lastname: Bender Kim
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sweet-Cordero
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Eckman
authors.forename: David A
authors.initials: DA
authors.lastname: Tuveson
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Capobianco
authors.forename: Victor L J
authors.initials: VL
authors.lastname: Tybulewicz
authors.forename: Tyler
authors.initials: T
authors.lastname: Jacks
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D018450:Disease Progression; D011905:Genes, ras / Q000502:physiology*; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009479:Neuropeptides / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000502:physiology*; D020830:rac1 GTP-Binding Protein