NF-kappa B Protects Human Papillomavirus Type 38 E6/E7-Immortalized Human Keratinocytes against Tumor Necrosis Factor Alpha and UV-Mediated Apoptosis

作者：Hussain Ishraq; Fathallah Ikbal; Accardi Rosita; Yue Jiping; Saidj Djamel; Shukla Ruchi; Hasan Uzma; Gheit Tarik; Niu Yamei; Tommasino Massimo^*; Sylla Bakary S

来源：Journal of Virology, 2011, 85(17): 9013-9022.

DOI：10.1128/JVI.00002-11

Constitutive activation of NF-kappa B 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-kappa B signaling in HPV38-induced cell growth transformation remains to be determined. In this study, we showed that HPV38 E6 and E7 activate NF-kappa B and that inhibition of the pathway with the I kappa B alpha superrepressor sensitizes HPV38E6E7-immortalized human keratinocytes to tumor necrosis factor alpha (TNF-alpha)- and UVB radiation-mediated apoptosis. Accordingly, inhibition of NF-kappa B signaling resulted in the downregulation of NF-kappa B-regulated antiapoptotic genes, including cIAP1, cIAP2, and xIAP genes. These findings demonstrate a critical role of NF-kappa B 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.

• 出版日期2011-9