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.
Copyright 2001 Wiley-Liss, Inc.
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