Expression of fas ligand in human hepatoma cell lines: Role of hepatitis-B virus X (HBx) in induction of Fas ligand

Abstract

It has been postulated that tumor cells expressing Fas ligand (FasL) can evade immune surveillance by inducing apoptosis in T cells expressing Fas. In this study, we investigated Fast expression in 13 human hepatoma cell lines. Strong Fast expression was detected by reverse transcription-polymerase chain reaction or immunofluorescence in Hep G2.2.15, in which the hepatitis-B-virus (HBV) genome was transfected, and in SNU-354, which showed HBx transcripts. To determine the biological activity of Fast, Hep G2.2.15 was co-cultured with MOLT-4, T-cell-leukemia cells. Hep G2.2.15 induced apoptosis in MOLT-4 and this was inhibited by the antagonistic anti-Fas antibody, ZB4. For further analysis of the role of HBx in the induction of Fast, PLC/PRF/5 cells were transfected transiently with the HBV genome, or HBx, or the frameshift mutant of HBx. In PLC/PRF/5 cells transfected with the HBV genome or HBx but not in cells transfected with the frameshift mutant of HBx, Fast expression was detected. Our data suggest that HBx plays a role in the induction of Fast in hepatoma cells and in the escape from immune surveillance. (C) 1999 Wiley-Liss, Inc.