title: Resistance to apoptosis of HPV 16-infected laryngeal cancer cells is associated with decreased Bak and increased Bcl-2 expression.
abstract: Human papillomavirus type 16 (HPV 16) plays an etiological role in human laryngeal carcinoma. Apoptosis is closely associated with various biological processes including oncogenesis. This study investigated how HPV 16 oncoproteins E6 and E7 affect apoptosis in human laryngeal cancer cells. We established two human laryngeal cancer cell lines that expressed HPV 16 E6 and E7, respectively. Using these two cell lines, we found that both E6 and E7 exhibited an inhibitive effect on apoptosis induced by tumor necrosis factor alpha and cycloheximide. In both transfected cell lines, the expression of pro-apoptotic Bak was reduced and that of anti-apoptotic Bcl-2 was over-expressed. However, the expression of caspase-3 and caspase-8 was not significantly different between the E6- and E7-transfected cells and the control cells without HPV 16. p53 Protein was not detected in either the transfected or the non-transfected cells. Our study indicates that: (1) HPV 16 E6 and E7 oncoproteins are capable of inhibiting apoptosis in laryngeal squamous carcinoma cells; (2) the mechanism modulated by E6 and E7 involves the over-expression of Bcl-2 and the down-regulation of Bak; (3) the anti-apoptotic pathway is not related to the level of p53, caspase-3, or caspase-8. These results suggest that the dysregulation of apoptotic molecules Bak and Bcl-2 by HPV 16 E6 and E7 plays a role in the prolongation of cell survival, which may subsequently contribute to the development of human laryngeal cancer.
authors.affiliation: Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Sir Y.K. Pao Center for Cancer, Shatin, N.T., Hong Kong, China.
authors.forename: J
authors.initials: J
authors.lastname: Du
authors.forename: G G
authors.initials: GG
authors.lastname: Chen
authors.forename: A C
authors.initials: AC
authors.lastname: Vlantis
authors.forename: P K S
authors.initials: PK
authors.lastname: Chan
authors.forename: R K Y
authors.initials: RK
authors.lastname: Tsang
authors.forename: C A
authors.initials: CA
authors.lastname: van Hasselt
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases / Q000096:biosynthesis / Q000187:drug effects; D045744:Cell Line, Tumor; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D007822:Laryngeal Neoplasms / Q000378:metabolism / Q000821:virology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000187:drug effects; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000503:physiopathology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000187:drug effects; D012097:Repressor Proteins; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000187:drug effects; D050998:bcl-2 Homologous Antagonist-Killer Protein
chemical_list: C494772:BAK1 protein, human; C068651:E6 protein, Human papillomavirus type 16; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011500:Protein Synthesis Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; C059731:oncogene protein E7, Human papillomavirus type 16; D003513:Cycloheximide; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases