Document Detail


Specific betapapillomaviruses associated with squamous cell carcinoma of the skin inhibit UVB-induced apoptosis of primary human keratinocytes.
MedLine Citation:
PMID:  18753241     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epidemiological studies have shown an association between infections by specific betapapillomaviruses, such as human papillomavirus (HPV) types 5 and 8, and cutaneous squamous cell carcinoma (SCC). The role of betapapillomaviruses in the development of cutaneous SCC is, however, still enigmatic. The ability to inhibit UVB-induced apoptosis, as demonstrated for HPV5 in vitro, may be important in this respect, as survival of DNA-damaged and mutated cells increases the risk of transformation. The aim of this study was to assess whether inhibition of UVB-induced apoptosis is a general property of betapapillomaviruses and to identify apoptotic factors that are potentially involved in this process. Primary human keratinocytes transduced with E6 and E7 of selected betapapillomaviruses (HPV5, HPV8, HPV15, HPV20, HPV24 and HPV38) were characterized and subjected to UVB irradiation. HPV8- and HPV20-expressing keratinocytes in particular showed fewer signs of apoptosis, as demonstrated by lower levels of active caspase 3, less enzymic caspase activity and less DNA fragmentation. The observed inhibition of UVB-induced apoptosis was mediated by E6 and coincided with reduced steady-state expression of the pro-apoptotic protein Bax. In conclusion, E6 of HPV8 and HPV20 reduces the apoptotic responses upon UVB irradiation when expressed in primary human keratinocytes. Infections with HPV8 and HPV20 may therefore augment the carcinogenic effect of UV radiation and potentially contribute to oncogenic transformation of the skin.
Authors:
Linda Struijk; Els van der Meijden; Siamaque Kazem; Jan ter Schegget; Frank R de Gruijl; Renske D M Steenbergen; Mariet C W Feltkamp
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of general virology     Volume:  89     ISSN:  0022-1317     ISO Abbreviation:  J. Gen. Virol.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-28     Completed Date:  2008-09-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077340     Medline TA:  J Gen Virol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2303-14     Citation Subset:  IM    
Affiliation:
Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / radiation effects
Betapapillomavirus / classification,  genetics,  pathogenicity*
Carcinoma, Squamous Cell / etiology,  pathology,  virology*
Caspase 3 / metabolism
Cells, Cultured
DNA Fragmentation
Gene Expression
Genes, Viral
Humans
Keratinocytes / pathology,  radiation effects*,  virology*
Oncogene Proteins, Viral / genetics
Papillomavirus Infections / complications,  pathology,  virology
Retinoblastoma Protein / metabolism
Skin Neoplasms / etiology,  pathology,  virology*
Transduction, Genetic
Tumor Suppressor Protein p53 / metabolism
Ultraviolet Rays
bcl-2 Homologous Antagonist-Killer Protein / metabolism
bcl-2-Associated X Protein / metabolism
bcl-X Protein / metabolism
Chemical
Reg. No./Substance:
0/BAK1 protein, human; 0/BAX protein, human; 0/BCL2L1 protein, human; 0/Oncogene Proteins, Viral; 0/Retinoblastoma Protein; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 0/bcl-2 Homologous Antagonist-Killer Protein; 0/bcl-2-Associated X Protein; 0/bcl-X Protein; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3

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