Expression of Fas-related genes in human hepatocellular carcinomas

Hepatocellular carcinoma (HCC) is one of the tumors known to be resistant to Fas-mediated apoptosis. To elucidate the possible mechanisms of this resistance, we examined the mRNA transcripts of genes related to Fas in 10 hepatitis B virus (HBV)-associated HCC cell lines and six HBV-associated HCC tissues. Most of the HBV-associated HCC cell lines showed markedly decreased Fas expression. Some cell lines expressed FAP, a possible inhibitor of apoptosis, or showed downregulated expression of FADD or FLICE, molecules essential to Fas-mediated apoptosis. All six HBV-associated HCC tissues also showed decreased Fas expression compared with their non-malignant counterparts. Our data demonstrate that HBV-associated HCC showed a common defect in the expression of Fas, upregulation of FAP and downregulation of downstream molecules such as FADD and FLICE.