H441 PULMONARY EPITHELIAL-CELL MITOGENIC EFFECTS AND SIGNALING PATHWAYS IN RESPONSE TO HGF AND TGF-ALPHA

Pulmonary epithelial cells are important in lung growth, development, and injury. H441 pulmonary adenocarcinoma cells may be a useful model for studying pulmonary epithelial cell growth factor responses in vitr o. Isolated pulmonary epithelial type II cells proliferate in response to transforming growth factor (TGF)-alpha via the epidermal growth fa ctor (EGF) receptor Type II cells also proliferate in response to hepa locyte growth factor (HGF). In the present study, H441 cell responses to these growth factors were examined, and compared to type II cells. Both the EGF-R and the c-met proto-oncogene receptor, to which HGF bin ds, we immunoprecipitated from H441 cells. In H441 cells, addition of TGF-alpha resulted in phosphorylation of the EGF receptor and increase d cell number and tritiated thymidine incorporation. Incubation with H GF resulted in phosphorylation of its c-met proto-oncogene receptor in type II and H441 cells, and also increased cell number and tritiated thymidine incorporation. Both HGF and TGF-alpha stimulated phosphoryla tion of the intracellular signaling molecules p42 and p44 mitogen acti vated protein kinases in H441 cells. H441 cells exhibited responses to mitogenic growth factors similar to type II cells and may be useful a s a model for type II cell growth factor responses and signal transduc tion.