Coexpression of the c-met proto-oncogene and hepatocyte growth factor in human pancreatic cancer.
The c-met proto-oncogene encodes a transmembrane tyrosine kinase receptor (MET) that has the capacity to modulate cell proliferation and differentiation; it is activated by the hepatocyte growth factor. Using a highly specific anti-MET antibody we found mild MET immunoreactivity in acinar, ductal, and islet cells in the normal human pancreas and intense MET immunoreactivity in many of the duct-like cancer cells in 14 of 16 human pancreatic adenocarcinomas. Intense MET immunoreactivity was also evident in the ductal cells in regions adjacent to the cancer cells. Northern blot analysis of total RNA revealed that, by comparison with the normal pancreas, pancreatic cancers exhibited a 7-fold (P < 0.01) increase in c-met mRNA levels. Hepatocyte growth factor mRNA levels were increased 10-fold (P < 0.05) in the same cancers. The concomitant over-expression of c-met and hepatocyte growth factor in human pancreatic cancers suggests that there is excessive activation of c-met-dependent signaling pathways that may contribute to pancreatic cancer cell growth in vivo.
Ebert
M
M
Department of Medicine, University of California, Irvine 92717.
Yokoyama
M
M
Friess
H
H
Büchler
M W
MW
Korc
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D005260:Female; D017228:Hepatocyte Growth Factor / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000737:chemistry*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019859:Proto-Oncogene Proteins c-met; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases