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

Scand J Gastroenterol. 2000 Jan;35(1):90-5. doi: 10.1080/003655200750024597.

Abstract

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-1alpha (IL-1alpha), IL-6, tumor necrosis factor-alpha (TNF-alpha) or transforming growth factor-beta1 (TGF-beta1). 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 and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Ceruletide
  • Cytokines / pharmacology
  • Cytokines / physiology*
  • Hepatocyte Growth Factor
  • Humans
  • Immunohistochemistry
  • Interleukin-1 / pharmacology
  • Interleukin-1 / physiology
  • Interleukin-6 / pharmacology
  • Interleukin-6 / physiology
  • Male
  • Pancreas / metabolism*
  • Pancreas / physiology
  • Pancreatic Neoplasms / metabolism*
  • Pancreatitis / chemically induced
  • Pancreatitis / metabolism*
  • Proto-Oncogene Proteins c-met / analysis*
  • Rats
  • Rats, Wistar
  • Regeneration
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta / physiology
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Hepatocyte Growth Factor
  • Ceruletide
  • Proto-Oncogene Proteins c-met