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Human papillomavirus type 16 E6‐enhanced susceptibility to apoptosis induced by TNF in A2780 human ovarian cancer cell line
Author(s) -
Vikhanskaya Faina,
Falugi Carla,
Valente Piera,
Russo Patrizia
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.10114
Subject(s) - apoptosis , cytotoxicity , cell culture , transfection , tumor necrosis factor alpha , cancer research , biology , dna fragmentation , ovarian cancer , programmed cell death , microbiology and biotechnology , cancer cell , in vitro , cancer , immunology , biochemistry , genetics
In our study, we show that expression of HPV‐16 E6 sensitizes TNF‐induced cytotoxicity of human ovarian cancer cell line A2780. This effect is not related to a different number of TNF receptors present on cell membrane. The major induction of massive apoptosis induced by TNF is not p53‐ and p21 waf‐1 ‐dependent but it is principally related to NF‐κB inhibition in A2780/E6 cells. Consistently to NF‐κB inhibition a rapidly release of cytochrome c and severe induction of DNA fragmentation are seen in A2780/E6 cells. Also in human colon cancer cell line HCT‐116/E6 the expression of HPV‐16 E6 enhances TNF‐cytotoxicity. This effect is not present in the HCT‐116/mu‐p53 clone (transfected with a dominant‐negative mutated p53 transgene). Thus, taken together all these observations suggest that HPV‐16 E6 sensitizes A2780 and HCT‐116 cells to TNF; this effect is not p53‐dependent, but it is essentially mediated through an inhibition in activating NF‐κB activities. © 2001 Wiley‐Liss, Inc.