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K-ras activation generates an inflammatory response in lung tumors
- Source :
- Oncogene. 25(14)
- Publication Year :
- 2005
-
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.
- Subjects :
- Cancer Research
Chemokine
Lung Neoplasms
Inflammation
medicine.disease_cause
Mice
Cell Line, Tumor
Macrophages, Alveolar
Genetics
medicine
Animals
Humans
Lung cancer
Molecular Biology
DNA Primers
Lung
biology
medicine.diagnostic_test
Base Sequence
Reverse Transcriptase Polymerase Chain Reaction
Pneumonia
respiratory system
medicine.disease
Immunohistochemistry
Mice, Mutant Strains
Bronchoalveolar lavage
medicine.anatomical_structure
Genes, ras
Tumor progression
Immunology
biology.protein
Cancer research
Adenocarcinoma
medicine.symptom
Carcinogenesis
Bronchoalveolar Lavage Fluid
Subjects
Details
- ISSN :
- 09509232
- Volume :
- 25
- Issue :
- 14
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....f82ef717bb2d148d1670bb1cb84e5a4a