title: NF-kappaB protects human papillomavirus type 38 E6/E7-immortalized human keratinocytes against tumor necrosis factor alpha and UV-mediated apoptosis.
abstract: Constitutive activation of NF-κB signaling is a key event in virus- and non-virus-induced carcinogenesis. We have previously reported that cutaneous human papillomavirus type 38 (HPV38) displays transforming properties in in vitro and in vivo experimental models. However, the involvement of NF-κB signaling in HPV38-induced cell growth transformation remains to be determined. In this study, we showed that HPV38 E6 and E7 activate NF-κB and that inhibition of the pathway with the IκBα superrepressor sensitizes HPV38E6E7-immortalized human keratinocytes to tumor necrosis factor alpha (TNF-α)- and UVB radiation-mediated apoptosis. Accordingly, inhibition of NF-κB signaling resulted in the downregulation of NF-κB-regulated antiapoptotic genes, including cIAP1, cIAP2, and xIAP genes. These findings demonstrate a critical role of NF-κB activity in the survival of HPV38E6E7-immortalized human keratinocytes exposed to cytokine or UV radiation. Our data provide additional evidence for cooperation between beta HPV infection and UV irradiation in skin carcinogenesis.
authors.affiliation: International Agency for Research on Cancer, 150 cours Albert-Thomas, 69372 Lyon Cedex 08, France.
authors.forename: Ishraq
authors.initials: I
authors.lastname: Hussain
authors.forename: Ikbal
authors.initials: I
authors.lastname: Fathallah
authors.forename: Rosita
authors.initials: R
authors.lastname: Accardi
authors.forename: Jiping
authors.initials: J
authors.lastname: Yue
authors.forename: Djamel
authors.initials: D
authors.lastname: Saidj
authors.forename: Ruchi
authors.initials: R
authors.lastname: Shukla
authors.forename: Uzma
authors.initials: U
authors.lastname: Hasan
authors.forename: Tarik
authors.initials: T
authors.lastname: Gheit
authors.forename: Yamei
authors.initials: Y
authors.lastname: Niu
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
authors.forename: Bakary S
authors.initials: BS
authors.lastname: Sylla
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000528:radiation effects*; D016328:NF-kappa B / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
chemical_list: D016328:NF-kappa B; D009856:Oncogene Proteins, Viral; D014409:Tumor Necrosis Factor-alpha