C-met protooncogene expression and its regulation by cytokines in the regenerating pancreas and in pancreatic cancer cells

Background: Activation of the receptor c-met stimulates motility, mitosis, morphogenesis, processes involved in organ regeneration, or progression of malignancies. In the present study we investigated the expression of c-met protein in the regenerating pancreas and characterized the influence of cytokines on c-met expression. Methods: Acute pancreatitis was induced in rats by cerulein injection. Rat acini and rat and human pancreatic cancer cells were stimulated with interleukin-1 alpha (IL-1 alpha), IL-6, tumor necrosis factor-beta(1) (TNF-alpha) or transforming growth factor-beta(1) (TGF-beta(1)). C-met expression was analyzed by means of Western blotting and localization in pancreatic tissue by immunohistochemistry. Results: C-met protein expression was significantly upregulated in the regenerating pancreas;lhd localized in areas of regenerating tissue. Stimulation with cytokines resulted in a two- to threefold increase of c-met expression in vitro. Conclusion: Enhanced c-met expression after acute pancreatitis suggests that HGF/met has an important role in pancreatic regeneration, which is probably mediated by cytokines. This regulatory mechanism is also of importance in pancreatic cancer.