title: Pten inactivation accelerates oncogenic K-ras-initiated tumorigenesis in a mouse model of lung cancer.
abstract: Phosphatase and tensin homologue deleted from chromosome 10 (Pten) is expressed aberrantly in non-small cell lung cancer cells, but the role of Pten in lung neoplasia has not been fully elucidated. In this study, we used a genetic approach to inactivate Pten in the bronchial epithelium of mice. Although, by itself, Pten inactivation had no discernible effect on bronchial epithelial histology, it accelerated lung tumorigenesis initiated by oncogenic K-ras, causing more rapid lethality than that induced by oncogenic K-ras alone (8 weeks versus 24 weeks of median duration of survival, respectively). Lung tumors arose in K-ras mutant, Pten-deficient mice that rapidly obstructed bronchial lumina and replaced alveolar spaces. Relative to K-ras mutant tumors, the K-ras mutant, Pten-deficient tumors exhibited more advanced histologic severity and more prominent inflammation and vascularity. Thus, Pten inactivation cooperated with oncogenic K-ras in promoting lung tumorigenesis.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, University of Texas-M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Iwanaga
authors.forename: Yanan
authors.initials: Y
authors.lastname: Yang
authors.forename: Maria Gabriela
authors.initials: MG
authors.lastname: Raso
authors.forename: Lijiang
authors.initials: L
authors.lastname: Ma
authors.forename: Amy E
authors.initials: AE
authors.lastname: Hanna
authors.forename: Nishan
authors.initials: N
authors.lastname: Thilaganathan
authors.forename: Seyed
authors.initials: S
authors.lastname: Moghaddam
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Evans
authors.forename: Huaiguang
authors.initials: H
authors.lastname: Li
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Cai
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Sato
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: Demayo
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Kurie
mesh_terms: D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000483:Alleles; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D011905:Genes, ras; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse