Dissociation of c-fos induction and mitogen-activated-protein kinase activation from the hepatocyte-growth-factor-induced motility response in human gastric carcinoma cells.
The function of hepatocyte growth factor/scatter factor (HGF/SF) is to increase proliferation as well as to stimulate motility and disperse cell colonies of epithelial cells. In this study, we examined the motogenic and mitogenic responses of two human gastric carcinoma cell types, MKN7 and MKN74. Cell motility of both cell lines was markedly stimulated by HGF/SF. In contrast, HGF/SF stimulated cell growth of MKN74 cells, but did not stimulate growth of MKN7 cells. To address the cause of the difference in response of these cells, which may reflect some differences in signaling pathways downstream from the HGF/SF receptor, c-Met, we investigated the induction of the proto-oncogene c-fos. The level of c-fos mRNA increased and reached a maximum approximately 40 min after HGF/SF stimulation in MKN74 cells, and thereafter its level rapidly decreased. In contrast, the level of c-fos expression was very low irrespective of the stimulation in MKN7 cells. c-Fos protein was transiently induced only in MKN74 cells l h after treatment with HGF/SF, and its levels subsequently decreased. We subsequently examined the activation of mitogen-activated-protein kinase, which is a major mediator in the signaling pathway leading to the stimulation of c-fos transcription, after HGF/SF treatment in both cell lines. Mitogen-activated-protein kinase was markedly activated by this treatment in MKN74 cells, but was only slightly activated in MKN7 cells. These results suggest that although mitogen-activated-protein kinase activation and c-fos induction play an essential role in the signaling pathway leading to cell growth, they are not required for the motility response induced by HGF/SF.
Nagamine
K
K
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Japan.
Shibamoto
S
S
Takeuchi
K
K
Miyazawa
K
K
Kitamura
N
N
Chatani
Y
Y
Kohno
M
M
Ito
F
F
D000230:Adenocarcinoma / Q000503:physiopathology*; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000503:physiopathology*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D009838:Oligodeoxyribonucleotides; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D017228:Hepatocyte Growth Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases