This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Iwanaga, K. Articles by Kurie, J. M. Search for Related Content PubMed PubMed Citation Articles by Iwanaga, K. Articles by Kurie, J. M.

Pten Inactivation Accelerates Oncogenic K-ras–Initiated Tumorigenesis in a Mouse Model of Lung Cancer

Departments of ¹ Thoracic/Head and Neck Medical Oncology, ² Pathology, and ³ Pulmonary Medicine, University of Texas-M. D. Anderson Cancer Center; Departments of ⁴ Molecular and Cellular Biology and ⁵ Molecular and Human Genetics and ⁶ Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas; ⁷ Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; and ⁸ Department of Molecular and Medical Pharmacology, University of California at Los Angeles, Los Angeles, California

Requests for reprints: Jonathan M. Kurie, Unit 432, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-6363; Fax: 713-792-1220; E-mail: jkurie{at}mdanderson.org.

Key Words: Pten • K-ras • lung cancer • mouse models

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. [Cancer Res 2008;68(4):1119–27]

This article has been cited by other articles:

				S. Regina, J.-B. Valentin, S. Lachot, E. Lemarie, J. Rollin, and Y. Gruel Increased Tissue Factor Expression Is Associated with Reduced Survival in Non-Small Cell Lung Cancer and with Mutations of TP53 and PTEN Clin. Chem., October 1, 2009; 55(10): 1834 - 1842. [Abstract] [Full Text] [PDF]

				K. A. Miller, N. Yeager, K. Baker, X.-H. Liao, S. Refetoff, and A. Di Cristofano Oncogenic Kras Requires Simultaneous PI3K Signaling to Induce ERK Activation and Transform Thyroid Epithelial Cells In vivo Cancer Res., April 15, 2009; 69(8): 3689 - 3694. [Abstract] [Full Text] [PDF]

				S. J. Moghaddam, H. Li, S.-N. Cho, M. K. Dishop, I. I. Wistuba, L. Ji, J. M. Kurie, B. F. Dickey, and F. J. DeMayo Promotion of Lung Carcinogenesis by Chronic Obstructive Pulmonary Disease-Like Airway Inflammation in a K-ras-Induced Mouse Model Am. J. Respir. Cell Mol. Biol., April 1, 2009; 40(4): 443 - 453. [Abstract] [Full Text] [PDF]

				D.M. Raiser, S.J. Zacharek, R.R. Roach, S.J. Curtis, K.W. Sinkevicius, D.W. Gludish, and C.F. Kim Stem Cell Biology in the Lung and Lung Cancers: Employing Pulmonary Context and Classic Approaches Cold Spring Harb Symp Quant Biol, November 26, 2008; (2008) sqb.2008.73.036v2. [Abstract] [PDF]