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

✍ Scribed by Adriana Aguilar-Lemarroy; Sabine Kirchhoff; Noel Whitaker; Patricio Gariglio; Harald zur Hausen; Peter H. Krammer; Frank Rösl

Publisher
John Wiley and Sons
Year
2001
Tongue
French
Weight
343 KB
Volume
93
Category
Article
ISSN
0020-7136

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✦ Synopsis

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.

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