Human papillomavirus type 16 E6-enhanced susceptibility to apoptosis induced by TNF in A2780 human ovarian cancer cell line
✍ Scribed by Faina Vikhanskaya; Carla Falugi; Piera Valente; Patrizia Russo
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- French
- Weight
- 538 KB
- Volume
- 97
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
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.