Mouse model for lung tumorigenesis through Cre/lox controlled sporadic activation of the K-Ras oncogene

Oncogene. 2001 Oct 4;20(45):6551-8. doi: 10.1038/sj.onc.1204837.


The onset of human lung cancer occurs through sequential mutations in oncogenes and tumor suppressor genes. Mutations in K-Ras play a prominent role in human non-small cell lung cancer. We have developed a mouse lung tumor model in which K-Ras can be sporadically activated through Cre-lox mediated somatic recombination. Adenoviral mediated delivery of Cre recombinase in lung epithelial cells gave rise to rapid onset of tumorigenesis, yielding pulmonary adenocarcinomas with 100% incidence after a short latency. The lung tumor lesions shared many features with human non-small cell lung cancer. Our data show that sporadic expression of the K-Ras oncogene is sufficient to elicit lung tumorigenesis. Therefore this model has many advantages over conventional transgenic models used thus far.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / etiology*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenoviridae / genetics
  • Alleles
  • Animals
  • Carcinoma, Non-Small-Cell Lung / etiology*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease Models, Animal*
  • Genes, Reporter
  • Genetic Vectors
  • Integrases / genetics*
  • Integrases / metabolism
  • Lung Neoplasms / etiology*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Transgenic
  • Oncogene Protein p21(ras) / biosynthesis
  • Oncogene Protein p21(ras) / genetics*
  • RNA, Neoplasm / biosynthesis
  • Recombination, Genetic
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism


  • RNA, Neoplasm
  • Viral Proteins
  • Cre recombinase
  • Integrases
  • Oncogene Protein p21(ras)