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-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.


CONCLUSIONS
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.
Otte
J M
JM
1st Dept. of Internal Medicine, Christian-Albrechts University, Kiel, Germany.
Kiehne
K
K
Schmitz
F
F
Fölsch
U R
UR
Herzig
K H
KH
D000208:Acute Disease; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002108:Ceruletide; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D017228:Hepatocyte Growth Factor; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology; D008297:Male; D010179:Pancreas / Q000378:metabolism* / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D017228:Hepatocyte Growth Factor; D002108:Ceruletide; D019859:Proto-Oncogene Proteins c-met