Differential sensitivity of human papillomavirus type 16 + and type 18 + cervical carcinoma cells to CD95‐mediated apoptosis

When cervical carcinoma cells were monitored for apoptotic signals, HPV18 + lines were found to be highly sensitive to agonistic CD95 antibodies or recombinant CD95 ligands after co‐exposure with CHX (CD95 S ). In contrast, HPV16 + cervical carcinoma cells and HPV16‐immortalized non‐malignant human keratinocytes were CD95‐resistant (CD95 R ) under equivalent conditions. Somatic cell hybridization between CD95 S and CD95 R cervical carcinoma cell lines revealed that CD95 sensitivity was a dominant trait, which could be correlated with abundant c‐Myc and low Bcl‐X L expression. Although CD95 R cervical carcinoma cells expressed even higher levels of p53 and CD95 receptor at the surface, resistance could be attributed to the inability to form a functional DISC, necessary for successful transmission of the apoptogenic response. These data indicate that resistance to apoptotic stimuli represents an important immunological escape mechanism during virus‐induced carcinogenesis. © 2001 Wiley‐Liss, Inc.