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

Kentaro Iwanaga, Yanan D 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

Research output: Contribution to journalArticle

85 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Lung Neoplasms
Carcinogenesis
Lung
Neoplasms
Chromosomes, Human, Pair 10
Phosphoric Monoester Hydrolases
Non-Small Cell Lung Carcinoma
Histology
Epithelium
Inflammation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pten inactivation accelerates oncogenic K-ras-initiated tumorigenesis in a mouse model of lung cancer. / Iwanaga, Kentaro; Yang, Yanan D; Raso, Maria Gabriela; Ma, Lijiang; Hanna, Amy E.; Thilaganathan, Nishan; Moghaddam, Seyed; Evans, Christopher M.; Li, Huaiguang; Cai, Wei Wen; Sato, Mitsuo; Minna, John D.; Wu, Hong; Creighton, Chad J.; Demayo, Francesco J.; Wistuba, Ignacio I.; Kurie, Jonathan M.

In: Cancer Research, Vol. 68, No. 4, 15.02.2008, p. 1119-1127.

Research output: Contribution to journalArticle

Iwanaga, K, Yang, YD, Raso, MG, Ma, L, Hanna, AE, Thilaganathan, N, Moghaddam, S, Evans, CM, Li, H, Cai, WW, Sato, M, Minna, JD, Wu, H, Creighton, CJ, Demayo, FJ, Wistuba, II & Kurie, JM 2008, 'Pten inactivation accelerates oncogenic K-ras-initiated tumorigenesis in a mouse model of lung cancer', Cancer Research, vol. 68, no. 4, pp. 1119-1127. https://doi.org/10.1158/0008-5472.CAN-07-3117
Iwanaga, Kentaro ; Yang, Yanan D ; Raso, Maria Gabriela ; Ma, Lijiang ; Hanna, Amy E. ; Thilaganathan, Nishan ; Moghaddam, Seyed ; Evans, Christopher M. ; Li, Huaiguang ; Cai, Wei Wen ; Sato, Mitsuo ; Minna, John D. ; Wu, Hong ; Creighton, Chad J. ; Demayo, Francesco J. ; Wistuba, Ignacio I. ; Kurie, Jonathan M. / Pten inactivation accelerates oncogenic K-ras-initiated tumorigenesis in a mouse model of lung cancer. In: Cancer Research. 2008 ; Vol. 68, No. 4. pp. 1119-1127.
@article{8afa529622f446a5aee91d6ced6e9418,
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.",
author = "Kentaro Iwanaga and Yang, {Yanan D} and Raso, {Maria Gabriela} and Lijiang Ma and Hanna, {Amy E.} and Nishan Thilaganathan and Seyed Moghaddam and Evans, {Christopher M.} and Huaiguang Li and Cai, {Wei Wen} and Mitsuo Sato and Minna, {John D.} and Hong Wu and Creighton, {Chad J.} and Demayo, {Francesco J.} and Wistuba, {Ignacio I.} and Kurie, {Jonathan M.}",
year = "2008",
month = "2",
day = "15",
doi = "10.1158/0008-5472.CAN-07-3117",
language = "English (US)",
volume = "68",
pages = "1119--1127",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "4",

}

TY - JOUR

T1 - Pten inactivation accelerates oncogenic K-ras-initiated tumorigenesis in a mouse model of lung cancer

AU - Iwanaga, Kentaro

AU - Yang, Yanan D

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.

UR - http://www.scopus.com/inward/record.url?scp=39449134253&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39449134253&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-07-3117

DO - 10.1158/0008-5472.CAN-07-3117

M3 - Article

C2 - 18281487

AN - SCOPUS:39449134253

VL - 68

SP - 1119

EP - 1127

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 4

ER -