K-ras activation generates an inflammatory response in lung tumors
| Autor: | David J. Sugarbaker, Thomas J. Mariani, A. M. Houghton, N. El-Bardeesy, Giovanni Tonon, Aram F. Hezel, Luiz A. Marconcini, Richard S. Maser, Hongbin Ji, Steven D. Shapiro, Kwok-Kin Wong, Roderick T. Bronson, Robert F. Padera, Kate McNamara, C. B. Kim, Samanthi A. Perera |
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| Přispěvatelé: | Ji, H, Houghton, Am, Mariani, Tj, Perera, S, Kim, Cb, Padera, R, Tonon, G, Mcnamara, K, Marconcini, La, Hezel, A, El-Bardeesy, N, Bronson, Rt, Sugarbaker, D, Maser, R, Shapiro, Sd, Wong, Kk |
| Rok vydání: | 2005 |
| Předmět: |
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 |
| Zdroj: | Oncogene. 25(14) |
| ISSN: | 0950-9232 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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