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Differential sensitivity of human papillomavirus type 16 + and type 18 + cervical carcinoma cells to CD95‐mediated apoptosis
Author(s) -
AguilarLemarroy Adriana,
Kirchhoff Sabine,
Whitaker Noel,
Gariglio Patricio,
zur Hausen Harald,
Krammer Peter H.,
Rösl Frank
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1405
Subject(s) - fas receptor , apoptosis , cancer research , biology , carcinoma , carcinogenesis , somatic cell , cell culture , immunology , programmed cell death , gene , genetics
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.