Pten inactivation accelerates oncogenic K-ras-initiated tumorigenesis in a mouse model of lung cancer.
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.
Iwanaga
Kentaro
K
Department of Thoracic/Head and Neck Medical Oncology, University of Texas-M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Yang
Yanan
Y
Raso
Maria Gabriela
MG
Ma
Lijiang
L
Hanna
Amy E
AE
Thilaganathan
Nishan
N
Moghaddam
Seyed
S
Evans
Christopher M
CM
Li
Huaiguang
H
Cai
Wei-Wen
WW
Sato
Mitsuo
M
Minna
John D
JD
Wu
Hong
H
Creighton
Chad J
CJ
Demayo
Francesco J
FJ
Wistuba
Ignacio I
II
Kurie
Jonathan M
JM
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
D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse