Inhibitory effect of hepatocyte growth factor against FaO hepatocellular carcinoma cells may be associated with changes of intracellular signalling pathways mediated by protein kinase C.
Hepatocyte growth factor (HGF) stimulates growth of mature hepatocytes, whereas it inhibits growth of cancer cells including hepatocellular carcinoma (HCC) cells. However, the regulatory mechanisms for this phenomenon remains unclear. An important intermediary in HGF signal transduction in normal hepatocytes, c-myc, was not induced in FaO HCC cells after HGF stimulation, suggesting that intracellular signalling pathways of HGF in FaO HCC cells were different from those in normal hepatocytes. Protein kinase C (PKC) has been reported to be involved in signalling pathways of many growth factors. To study whether PKC is associated with this inhibitory mechanism, we studied the effects of HGF and/or 12-O-tetradecanoyl phorbol-13-acetate (TPA) on the growth of normal hepatocytes and FaO HCC cells. Consequently, HGF or TPA stimulated growth of normal hepatocytes, while equal doses of TPA or HGF inhibited growth of FaO HCC cells, respectively. In addition, TPA reversed the HGF effect in both normal hepatocytes and FaO HCC cells. These data suggest that an inhibitory effect of HGF on FaO HCC cells may be associated with changes of protein kinase C-mediated intracellular signalling pathways.
Shiota
G
G
Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
Kawasaki
H
H
Nakamura
T
T
Schmidt
E V
EV
D000818:Animals; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004338:Drug Combinations; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004338:Drug Combinations; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D004247:DNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate