Human papillomavirus type 16 E6-enhanced susceptibility to apoptosis induced by TNF in A2780 human ovarian cancer cell line

Int J Cancer. 2002 Feb 20;97(6):732-9. doi: 10.1002/ijc.10114.

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-kappaB inhibition in A2780/E6 cells. Consistently to NF-kappaB 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-kappaB activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism
  • Cytochrome c Group / metabolism
  • DNA, Neoplasm / metabolism
  • Electrophoretic Mobility Shift Assay
  • Female
  • Flow Cytometry
  • Genes, myc / physiology
  • Humans
  • Interleukin-6 / metabolism
  • Mitochondria / metabolism
  • NF-kappa B / genetics
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Repressor Proteins*
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Cytochrome c Group
  • DNA, Neoplasm
  • E6 protein, Human papillomavirus type 16
  • Interleukin-6
  • NF-kappa B
  • Oncogene Proteins, Viral
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor
  • Repressor Proteins
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53