Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
Status of p53 and WAF1/CIP1 in anogenital lesions harboring human papillomavirus and human immunodeficiency virus (Meeting abstract).
Proc Annu Meet Am Assoc Cancer Res; 38:A1063 1997. Unique Identifier : AIDSLINE ICDB/98638063 Arany I; Yen A; Tyring SK; Department of Microbiology and Immunology, University of Texas; Medical Branch, Galveston, TX
Abstract:
Human papillomaviruses (HPVs) express various gene products, such as E6 protein which complexes with the p53 tumor suppressor protein and therefore diminishes p53-related regulatory mechanisms. Furthermore, HIV infection is believed to activate latent HPV infection and transcription. Accordingly, we carried out experiments on biopsies originated from condylomas ('low risk' HPVs), HIV-positive condylomas (infection with multiple 'low risk' and 'high risk' HPVs) and anogenital squamous cell carcinomas (SCCs, 'high risk' HPV infection). Using reverse-transcription PCR (RT-PCR) and Western immunoblotting, mRNA and protein levels of p53 and genes regulated by p53, such as mdm2 and WAF1/CIP1 were determined. We found that the presence of HPV can diminish p53 and increase WAF1/CIP1 and mdm2 protein levels. There were no significant differences in this regulation between 'low risk' and 'high risk' lesions. Our data suggest that these HPV-mediated cellular effects are not type-specific, and they might be part of a viral-cell interaction or represent a cellular defense mechanism against the virus. However, HIV-seropositivity renders HPV lesions containing both 'low risk' and 'high risk' significantly different. This may be due to the alteration of HPV-controlling cellular pathways by HIV tat and/or activation of cellular pathways different from HIV-negative counterparts. Either possibility has great interest and needs further verification.
Keywords: Anus Neoplasms/*VIROLOGY Carcinoma, Squamous Cell/*VIROLOGY Cyclins/*GENETICS/METABOLISM Genes, p53/GENETICS Genital Neoplasms, Female/*VIROLOGY HIV-1/*GENETICS Human Papillomavirus, Human/*GENETICS Protein p53/METABOLISM Proto-Oncogene Proteins/GENETICS/METABOLISM ABSTRACT 980228
M9820763
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