Dominant nature of the resistance to Fas- and tumor necrosis factor-alpha-mediated apoptosis in human prostatic carcinoma cell lines.

Abstract

We have recently found (O. W. Rokhlin et al., Cancer Res., 57: 1758-1768, 1997) that, although Fas ligation induced apoptosis in two of six human prostatic carcinoma cell lines investigated, the apoptotic machinery involved in Fas-mediated killing is already in place in Fas-resistant cell lines. Here, we investigated Fas- and tumor necrosis factor-alpha (TNF-alpha)-mediated apoptosis in cell hybrids between resistant (DU145 and JCA1) and sensitive (ALVA31 and PC3) cell lines. All three types of hybrid cells investigated, F1(DU145 x PC3), F1(JCA1 x PC3), and F1(JCA1 x ALVA31), were found to be resistant to Fas- and TNF-alpha-mediated apoptosis at the same level as the corresponding parental resistant cell lines. These results indicate that resistance to Fas- and TNF-alpha-mediated apoptosis dominates over sensitivity in cell hybrids and suggest that resistance may be regulated by an apoptosis suppressor factor or factors acting in resistant but not in sensitive cells.