P53, WAF1 CIP1 AND MDM2 EXPRESSION IN SKIN-LESIONS ASSOCIATED WITH HUMAN PAPILLOMAVIRUS AND HUMAN-IMMUNODEFICIENCY-VIRUS/

Human papillomaviruses (HPVs) express various gene products, such as E 6 protein which complexes with the p53 tumor suppressor protein and th erefore diminishes p53-related regulatory mechanisms This interaction is assumed to be HPV type-specific as ''high risk' or oncogenic HPV ty pes have more affinity for p53 binding than their ''low risk'' or non- oncogenic counterparts Furthermore, HN infection is believed to activa te latent HPV infection and transcription via direct and indirect inte raction with HPVs as well as cellular genes and functions. Accordingly we carried out experiments on biopsies which originated from condylom as (''low risk'' HPVs), HIV-positive condylomas (infection with multip le ''low risk'' and ''high risk'' HPVs) and anogenital squamous cell c arcinomas (SCCs, ''high risk'' HPV infection). Using reverse transcrip tion PCR (RT-PCR) and western immunoblotting, mRNA and protein levels of p53 and genes regulated by p53, such as mdm2 and WAF1/CIP1 were det ermined. We found that the presence of HPV can diminish p53 and increa se WAF1/CIP1 and mdm2 protein levels. There were no significant differ ences in this regulation between ''low risk'' and ''high risk'' lesion s. Our data suggest that these HPV-mediated cellular effects are not t ype-specific, and they might be part of a viral-cell interaction or re present a cellular defense mechanism against the virus. However; HIV-s eropositivity renders HPV lesions containing both ''low risk'' and ''h igh risk'' significantly different. This may be doe to the alteration of HPV-controlling cellular pathways by HN tat and/or activation of ce llular pathways different from HIV-negative counterparts. Either possi bility is of great interest and needs further verification.