A mutant epidermal growth factor receptor targeted to lung epithelium inhibits asbestos-induced proliferation and proto-oncogene expression

Christopher B Manning, Andrew B Cummins, Michael W Jung, Ingrid Berlanger, Cynthia R Timblin, Cathy Palmer, Douglas J Taatjes, David Hemenway, Pamela Vacek, Brooke T Mossman
2002 Cancer Research  
Asbestos is a ubiquitous naturally occurring fiber causing multiple cancers and fibroproliferativedisease. The mechanisms of epithelial cell hyperplasia, a hallmark of the initiation of lung cancers by asbestos, have been unclear. We demonstrate here that mice expressing a dominant-negative mutant epidermal growth factor receptor (EGFR) under the control of the human lung surfactant protein-C promoter exhibit decreased pulmonary epithelial cell proliferation without alterations in
more » ... ed inflammation. In contrast to transgene-negative littermates, inhalation of asbestos by mice expressing the mutant EGFR does not result in early and elevated expression of early response proto-oncogenes (fos/jun or activator protein 1 family members). Additionally, quantitative reverse transcriptase-PCR analysis for levels of c-jun and c-fos in bronchiolar epithelium isolated by laser capture microdissection demonstrates increases in expression of these genes in asbestos-exposed epithelial cells. Results show that the EGFR mediates both asbestos-induced proto-oncogene expression and epithelial cell proliferation, providing a rationale for modification of its phosphorylation in preventive and therapeutic approaches to lung cancers and mesothelioma.
pmid:12154012 fatcat:sbyjab54hvgsxfikp4cuykcz74