Pten inactivation accelerates oncogenic K-ras-initiated tumorigenesis in a mouse model of lung cancer

Kentaro Iwanaga, Yanan Yang, Maria Gabriela Raso, Lijiang Ma, Amy E. Hanna, Nishan Thilaganathan, Seyed Moghaddam, Christopher M. Evans, Huaiguang Li, Wei Wen Cai, Mitsuo Sato, John D. Minna, Hong Wu, Chad J. Creighton, Francesco J. Demayo, Ignacio I. Wistuba, Jonathan M. Kurie

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87 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1119-1127
Number of pages9
JournalCancer research
Volume68
Issue number4
DOIs
StatePublished - Feb 15 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Iwanaga, K., Yang, Y., Raso, M. G., Ma, L., Hanna, A. E., Thilaganathan, N., Moghaddam, S., Evans, C. M., Li, H., Cai, W. W., Sato, M., Minna, J. D., Wu, H., Creighton, C. J., Demayo, F. J., Wistuba, I. I., & Kurie, J. M. (2008). Pten inactivation accelerates oncogenic K-ras-initiated tumorigenesis in a mouse model of lung cancer. Cancer research, 68(4), 1119-1127. https://doi.org/10.1158/0008-5472.CAN-07-3117