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.
Aguilar-Lemarroy
A
A
Forschungsschwerpunkt Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Kirchhoff
S
S
Whitaker
N
N
Gariglio
P
P
zur Hausen
H
H
Krammer
P H
PH
Rösl
F
F
D017209:Apoptosis; D015153:Blotting, Western; D002277:Carcinoma / Q000473:pathology* / Q000821:virology*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002469:Cell Separation; D003513:Cycloheximide / Q000494:pharmacology; D053938:DNA Fragmentation; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005260:Female; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D027383:Papillomaviridae / Q000378:metabolism*; D010641:Phenotype; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D012680:Sensitivity and Specificity; D013997:Time Factors; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology*; D019014:fas Receptor / Q000096:biosynthesis* / Q000378:metabolism
D008024:Ligands; D011500:Protein Synthesis Inhibitors; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D003513:Cycloheximide; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases