Human papillomavirus type 16 E6-enhanced susceptibility to apoptosis induced by TNF in A2780 human ovarian cancer cell line.
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.
Vikhanskaya
Faina
F
Molecular Pathology Section, Laboratory of Experimental Oncology, National Institute for Research on Cancer, Genoa, Italy.
Falugi
Carla
C
Valente
Piera
P
Russo
Patrizia
P
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005434:Flow Cytometry; D016259:Genes, myc / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012097:Repressor Proteins; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D003574:Cytochrome c Group; D004273:DNA, Neoplasm; C068651:E6 protein, Human papillomavirus type 16; D015850:Interleukin-6; D016328:NF-kappa B; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D012097:Repressor Proteins; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53