Fas stimulation activates NF-kappaB in SK-Hep1 hepatocellular carcinoma cells.

Abstract

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.

• Authors: Hiroshi Okano, Katsuya Shiraki, Hidekazu Inoue, Tomoyuki Kawakita, Yukiko Saitou, Naoyuki Enokimura, Norihiko Yamamoto, Kazushi Sugimoto, Kazumoto Murata, Takeshi Nakano
• Journal: Oncology reports (Oncol Rep) 2003 Sep-Oct Vol. 10 Issue 5 Pg. 1145-8 ISSN: 1021-335X [Print] Greece
• PMID: 12883671 (Publication Type: Journal Article)

Chemical References

• FASLG protein, human
• Fas Ligand Protein
• Membrane Glycoproteins
• NF-kappa B
• Protein Synthesis Inhibitors
• fas Receptor
• Cycloheximide
• Luciferases

Topics

• Apoptosis
• Carcinoma, Hepatocellular (metabolism)
• Cell Division
• Cell Line, Tumor
• Cell Nucleus (metabolism)
• Cell Survival
• Cycloheximide (pharmacology)
• Dose-Response Relationship, Drug
• Enzyme Activation
• Fas Ligand Protein
• Genes, Reporter
• Humans
• Luciferases (metabolism)
• Lymphocytes (metabolism)
• Membrane Glycoproteins (metabolism)
• NF-kappa B (metabolism)
• Protein Synthesis Inhibitors (pharmacology)
• Signal Transduction
• fas Receptor (metabolism)