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 (CD95S). In contrast, HPV16+ cervical carcinoma cells and HPV16‐immortalized non‐malignant human kera...

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Bibliographic Details
Published in:International journal of cancer 2001-09, Vol.93 (6), p.823-831
Main Authors: Aguilar‐Lemarroy, Adriana, Kirchhoff, Sabine, Whitaker, Noel, Gariglio, Patricio, zur Hausen, Harald, Krammer, Peter H., Rösl, Frank
Format: Article
Language:English
Subjects:
Apoptosis
Biological and medical sciences
Blotting, Western
Carcinoma - pathology
Carcinoma - virology
Caspase 3
Caspase 8
Caspase 9
Caspases - metabolism
CD95
Cell Separation
cervical cancer
Cycloheximide - pharmacology
DNA Fragmentation
Down-Regulation
Electrophoresis, Polyacrylamide Gel
Enzyme Activation
fas Receptor - biosynthesis
fas Receptor - metabolism
Female
Female genital diseases
Flow Cytometry
Gynecology. Andrology. Obstetrics
HeLa Cells
human papillomavirus
Humans
immunological surveillance
Jurkat Cells
Ligands
Medical sciences
Membrane Potentials
Mitochondria - metabolism
Papillomaviridae - metabolism
Phenotype
Protein Synthesis Inhibitors - pharmacology
Recombinant Proteins - metabolism
Sensitivity and Specificity
somatic cell hybrids
Time Factors
Tumor Cells, Cultured
Tumor Suppressor Protein p53 - biosynthesis
Tumors
Uterine Cervical Neoplasms - pathology
Uterine Cervical Neoplasms - virology
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Summary: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 (CD95S). In contrast, HPV16+ cervical carcinoma cells and HPV16‐immortalized non‐malignant human keratinocytes were CD95‐resistant (CD95R) under equivalent conditions. Somatic cell hybridization between CD95S and CD95R cervical carcinoma cell lines revealed that CD95 sensitivity was a dominant trait, which could be correlated with abundant c‐Myc and low Bcl‐XL expression. Although CD95R 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.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.1405