RESUMEN

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.

Asunto(s)

Transformación Celular Viral , Papillomavirus Humano 16/patogenicidad , FN-kappa B/antagonistas & inhibidores , Proteínas Oncogénicas Virales/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Proteínas Represoras/metabolismo , Células Cultivadas , Cuello del Útero/citología , Cuello del Útero/metabolismo , Cuello del Útero/virología , Células Epiteliales/metabolismo , Células Epiteliales/virología , Femenino , Prepucio/citología , Prepucio/virología , Regulación de la Expresión Génica , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/crecimiento & desarrollo , Papillomavirus Humano 16/metabolismo , Humanos , Masculino , FN-kappa B/metabolismo , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus/genética , Proteínas Represoras/genética