title: Human papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization.
abstract: The NF-kB family of transcription factors regulates important biological functions including cell growth, survival and the immune response. We found that Human Papillomavirus type 16 (HPV-16) E7 and E6/E7 proteins inhibited basal and TNF-alpha-inducible NF-kB activity in human epithelial cells cultured from the cervical transformation zone, the anatomic region where most cervical cancers develop. In contrast, HPV-16 E6 regulated NF-kB in a cell type- and cell growth-dependent manner. NF-kB influenced immortalization of cervical cells by HPV16. Inhibition of NF-kB by an IkB alpha repressor mutant increased colony formation and immortalization by HPV-16. In contrast, activation of NF-kB by constitutive expression of p65 inhibited proliferation and immortalization. Our results suggest that inhibition of NF-kB by HPV-16 E6/E7 contributes to immortalization of cells from the cervical transformation zone.
authors.affiliation: Department of Biology, Clarkson University, Potsdam, NY 13699-5805, USA.
authors.forename: Erik R
authors.initials: ER
authors.lastname: Vandermark
authors.forename: Krysta A
authors.initials: KA
authors.lastname: Deluca
authors.forename: Courtney R
authors.initials: CR
authors.lastname: Gardner
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Marker
authors.forename: Cynthia N
authors.initials: CN
authors.lastname: Schreiner
authors.forename: David A
authors.initials: DA
authors.lastname: Strickland
authors.forename: Katelynn M
authors.initials: KM
authors.lastname: Wilton
authors.forename: Sumona
authors.initials: S
authors.lastname: Mondal
authors.forename: Craig D
authors.initials: CD
authors.lastname: Woodworth
mesh_terms: D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology / Q000378:metabolism / Q000821:virology; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D005260:Female; D052816:Foreskin / Q000166:cytology / Q000821:virology; D005786:Gene Expression Regulation; D052162:Human papillomavirus 16 / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D016328:NF-kappa B; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16