K-ras activation generates an inflammatory response in lung tumors.
Document Type
Article
Publication Date
2006
First Page
2105
Last Page
2112
JAX Source
Oncogene 2006 Mar; 25(14):2105-12.
Abstract
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.
Recommended Citation
Ji H,
Houghton AM,
Mariani TJ,
Perera S,
Kim CB,
Padera R,
Tonon G,
McNamara K,
Marconcini LA,
Hezel A,
El BN,
Bronson RT,
Sugarbaker D,
Maser RS,
Shapiro SD,
Wong KK.
K-ras activation generates an inflammatory response in lung tumors. Oncogene 2006 Mar; 25(14):2105-12.