DOMINANT NATURE OF THE RESISTANCE TO FAS-MEDIATED AND TUMOR NECROSIS FACTOR-ALPHA-MEDIATED APOPTOSIS IN HUMAN PROSTATIC-CARCINOMA CELL-LINES

We have recently found (O. W. Rokhlin et al., Cancer Res., 57: 1758-17 68, 1997) that, although Fas ligation induced apoptosis in tno of six human prostatic carcinoma cell lines investigated, the apoptotic machi nery involved in Fas-mediated killing is already in place in Fas-resis tant 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-alph a-mediated apoptosis at the same level as the corresponding parental r esistant cell lines, These results indicate that resistance to Fas- an d TNF-alpha-mediated apoptosis dominates over sensitivity in cell hybr ids and suggest that resistance may be regulated by an apoptosis suppr essor factor or factors acting in resistant but not in sensitive cells .