K-ras activation generates an inflammatory response in lung tumors

H. Ji, A. M. Houghton, T. J. Mariani, S. Perera, C. B. Kim, R. Padera, G. Tonon, K. McNamara, L. A. Marconcini, A. Hezel, N. El-Bardeesy, R. T. Bronson, D. Sugarbaker, R. S. Maser, S. D. Shapiro, K. K. Wong

Research output: Contribution to journalArticlepeer-review

235 Scopus citations


Activating mutations in K-ras are one of the most common genetic alterations in human lung cancer. To dissect the role of K-ras activation in bronchial epithelial cells during lung tumorigenesis, we created a model of lung adenocarcinoma by generating a conditional mutant mouse with both Clara cell secretory protein (CC10)-Cre recombinase and the Lox-Stop-Lox K-ras G12D alleles. The activation of K-ras mutant allele in CC10 positive cells resulted in a progressive phenotype characterized by cellular atypia, adenoma and ultimately adenocarcinoma. Surprisingly, K-ras activation in the bronchiolar epithelium is associated with a robust inflammatory response characterized by an abundant infiltration of alveolar macrophages and neutrophils. These mice displayed early mortality in the setting of this pulmonary inflammatory response with a median survival of 8 weeks. Bronchoalveolar lavage fluid from these mutant mice contained the MIP-2, KC, MCP-1 and LIX chemokines that increased significantly with age. Cell lines derived from these tumors directly produced MIP-2, LIX and KC. This model demonstrates that K-ras activation in the lung induces the elaboration of inflammatory chemokines and provides an excellent means to further study the complex interactions between inflammatory cells, chemokines and tumor progression.

Original languageEnglish
Pages (from-to)2105-2112
Number of pages8
Issue number14
StatePublished - 30 Mar 2006
Externally publishedYes


  • Inflammation
  • K-ras
  • Lung cancer
  • Macrophages
  • Neutrophils


Dive into the research topics of 'K-ras activation generates an inflammatory response in lung tumors'. Together they form a unique fingerprint.

Cite this