Cigarette Smoke Activates the Proto-Oncogene c-Src to Promote Airway Inflammation and Lung Tissue Destruction

• Published in: American journal of respiratory cell and molecular biology Vol. 50; no. 3; pp. 559 - 570
• Main Authors: Geraghty, Patrick, Hardigan, Andrew, Foronjy, Robert F.
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.03.2014
• Subjects: Animals; Case-Control Studies; Cell adhesion & migration; Cell culture; Cells, Cultured; Chronic obstructive pulmonary disease; Cigarettes; Cytokines - metabolism; Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Activation; Epidermal growth factor; Epithelial Cells - drug effects; Epithelial Cells - enzymology; Epithelial Cells - pathology; Humans; Inflammation Mediators - metabolism; Kinases; Lung - drug effects; Lung - enzymology; Lung - pathology; Lung cancer; Macrophages - drug effects; Macrophages - enzymology; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases - metabolism; Monocytes - drug effects; Monocytes - enzymology; Mortality; Neutrophils - drug effects; Neutrophils - enzymology; Original Research; Phosphorylation; Pneumonia - enzymology; Pneumonia - etiology; Pneumonia - genetics; Pneumonia - pathology; Pneumonia - prevention & control; Protein Kinase C-alpha - metabolism; Protein Kinase Inhibitors - pharmacology; Proteins; Proto-Oncogene Proteins c-raf - metabolism; Proto-Oncogene Proteins pp60(c-src) - antagonists & inhibitors; Proto-Oncogene Proteins pp60(c-src) - genetics; Proto-Oncogene Proteins pp60(c-src) - metabolism; Pulmonary Disease, Chronic Obstructive - enzymology; Pulmonary Disease, Chronic Obstructive - etiology; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - pathology; Pulmonary Disease, Chronic Obstructive - prevention & control; Receptor, Epidermal Growth Factor - metabolism; RNA Interference; Signal transduction; Signal Transduction - drug effects; Smoke - adverse effects; Smoking - adverse effects; Studies; Time Factors; Transfection

The diagnosis of chronic obstructive pulmonary disease (COPD) confers a 2-fold increased lung cancer risk even after adjusting for cigarette smoking, suggesting that common pathways are operative in both diseases. Although the role of the tyrosine kinase c-Src is established in lung cancer, less is...