Fas stimulation activates NF-kappaB in SK-Hep1 hepatocellular carcinoma cells.
The TNF-receptor family has a dual signaling pathway, including induction of apoptosis and NF-kappaB activation associated with cell survival. Hepatocellular carcinoma (HCC) cells express TNF-receptor family members and the signaling from these receptors induces NF-kappaB activation. However, the role of Fas in induction of NF-kappaB activation in HCC cells is not well understood. In this study, SK-Hep1, HepG2 or HLE cells were stimulated by anti-Fas agonistic antibody. Fas stimulation induced NF-kappaB activation in a dose-dependent manner in SK-Hep1 and HepG2 cell lines, but not in HLE cells. Anti-Fas agonistic antibody or the metabolic inhibitor, cyclo-heximide (CHX), failed to kill SK-Hep1 cells, but co-incubation with anti-Fas agonistic antibody and CHX was effective for induction of apoptosis. SK-Hep1 cell lines receiving Fas stimulation had increased viability, but the extent of cell proliferation was not dose-dependent. The observation suggests that Fas stimulation may contribute to HCC cell survival or proliferation.
Okano
Hiroshi
H
First Department of Internal Medicine, Mie University School of Medicine, Mie 514-8507, Japan.
Shiraki
Katsuya
K
Inoue
Hidekazu
H
Kawakita
Tomoyuki
T
Saitou
Yukiko
Y
Enokimura
Naoyuki
N
Yamamoto
Norihiko
N
Sugimoto
Kazushi
K
Murata
Kazumoto
K
Nakano
Takeshi
T
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002455:Cell Division; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D053222:Fas Ligand Protein; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011500:Protein Synthesis Inhibitors; D019014:fas Receptor; D003513:Cycloheximide; D008156:Luciferases