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Specific betapapillomaviruses associated with squamous cell carcinoma of the skin inhibit UVB-induced apoptosis of primary human keratinocytes.
Specific betapapillomaviruses associated with squamous cell carcinoma of the skin inhibit UVB-induced apoptosis of primary human keratinocytes.
- Source :
-
The Journal of general virology [J Gen Virol] 2008 Sep; Vol. 89 (Pt 9), pp. 2303-2314. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Apoptosis radiation effects
Betapapillomavirus classification
Betapapillomavirus genetics
Carcinoma, Squamous Cell etiology
Carcinoma, Squamous Cell pathology
Caspase 3 metabolism
Cells, Cultured
DNA Fragmentation
Gene Expression
Genes, Viral
Humans
Keratinocytes pathology
Oncogene Proteins, Viral genetics
Papillomavirus Infections complications
Papillomavirus Infections pathology
Papillomavirus Infections virology
Retinoblastoma Protein metabolism
Skin Neoplasms etiology
Skin Neoplasms pathology
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
Betapapillomavirus pathogenicity
Carcinoma, Squamous Cell virology
Keratinocytes radiation effects
Keratinocytes virology
Skin Neoplasms virology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1317
- Volume :
- 89
- Issue :
- Pt 9
- Database :
- MEDLINE
- Journal :
- The Journal of general virology
- Publication Type :
- Academic Journal
- Accession number :
- 18753241
- Full Text :
- https://doi.org/10.1099/vir.0.83317-0