TY - JOUR
T1 - Pten inactivation accelerates oncogenic K-ras-initiated tumorigenesis in a mouse model of lung cancer
AU - Iwanaga, Kentaro
AU - Yang, Yanan
AU - Raso, Maria Gabriela
AU - Ma, Lijiang
AU - Hanna, Amy E.
AU - Thilaganathan, Nishan
AU - Moghaddam, Seyed
AU - Evans, Christopher M.
AU - Li, Huaiguang
AU - Cai, Wei Wen
AU - Sato, Mitsuo
AU - Minna, John D.
AU - Wu, Hong
AU - Creighton, Chad J.
AU - Demayo, Francesco J.
AU - Wistuba, Ignacio I.
AU - Kurie, Jonathan M.
PY - 2008/2/15
Y1 - 2008/2/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-07-3117
DO - 10.1158/0008-5472.CAN-07-3117
M3 - Article
C2 - 18281487
AN - SCOPUS:39449134253
SN - 0008-5472
VL - 68
SP - 1119
EP - 1127
JO - Cancer research
JF - Cancer research
IS - 4
ER -