EurekaMag.com logo
+ Site Statistics
References:
52,725,316
Abstracts:
28,411,598
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

p53, WAF1/CIP1 and mdm2 expression in skin lesions associated with human papillomavirus and human immunodeficiency virus


Anticancer Research 17(2b): 1281-1285
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 E6 protein which complexes with the p53 tumor suppressor protein and therefore diminishes p53-related regulatory mechanisms. This interaction is assumed to be HPV type-specific as "high risk" or oncogenic HPV types have more affinity for p53 binding than their "low risk" or non-oncogenic counterparts. Furthermore, HIV infection is believed to activate latent HPV infection and transcription via direct and indirect interaction with HPVs as well as cellular genes and functions. Accordingly, we carried out experiments on biopsies which 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 is of great interest and needs further verification.


Accession: 002914319

PMID: 9137486



Related references

Status of p53 and WAF1/CIP1 in anogenital lesions harboring human papillomavirus and human immunodeficiency virus. Proceedings of the American Association for Cancer Research Annual Meeting 38(0): 158-159, 1997

Expression of P21 WAF1/CIP1 in human astrocytomas in correlating with P53, MDM2, and cellular proliferation index. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae 23(4): 341-345, 2003

Human papillomavirus infection in actinic keratosis and bowen's disease: comparative study with expression of cell-cycle regulatory proteins p21(Waf1/Cip1), p53, PCNA, Ki-67, and Bcl-2 in positive and negative lesions. Human Pathology 34(9): 886-892, 2003

Effect of actinomycin-d on the cell-cycle progression and the expression of p53, waf1/cip1, gadd45, and mdm-2 genes in human oral keratinocytes - implication of human papillomavirus infection. International Journal of Oncology 5(5): 1023-1030, 1994

The p21(WAF1/CIP1) promoter is methylated in Rat-1 cells: stable restoration of p53-dependent p21(WAF1/CIP1) expression after transfection of a genomic clone containing the p21(WAF1/CIP1) gene. Molecular and Cellular Biology 20(4): 1291-1298, 2000

High expression of MDM2 protein and low rate of p21(WAF1/CIP1) expression in SCID mice Epstein Barr virus-induced lymphoproliferation. Journal of Histochemistry and Cytochemistry 47(10): 1315-1322, 1999

P21-WAF1/CIP1 and MDM2 expression in non-Hodgkin's lymphoma and their relationship to p53 status: A p53+, MDM2-, p21- immunophenotype associated with missense p53 mutations. Journal of Pathology 181(1): 51-61, 1997

Growth factor receptor expression in anal squamous lesions: modifications associated with oncogenic human papillomavirus and human immunodeficiency virus. Human Pathology 40(11): 1517-1527, 2009

The hinge region of the human papillomavirus type 8 E2 protein activates the human p21(WAF1/CIP1) promoter via interaction with Sp1. Journal of General Virology 83(Pt 3): 503-510, 2002

Transcriptional activation of p21(waf1/cip1) by alkylphospholipids: role of the mitogen-activated protein kinase pathway in the transactivation of the human p21(waf1/cip1) promoter by Sp1. Cancer Research 64(2): 743-750, 2004