Differential In Vitro Immortalization Capacity of Eleven, Probable High-Risk Human Papillomavirus Types
| Autor: | Renske D.M. Steenbergen, Leontien Bosch, Duco Kramer, Denise M. Schutze, Peter J.F. Snijders, Chris J.L.M. Meijer |
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| Přispěvatelé: | Pathology, CCA - Oncogenesis |
| Rok vydání: | 2014 |
| Předmět: |
Senescence
Keratinocytes Male EXPRESSION Telomerase Immunology Foreskin Biology Alphapapillomavirus Cervical intraepithelial neoplasia Microbiology HPV E6 PROTEINS Transformation and Oncogenesis P53 DEGRADATION Virology TELOMERASE medicine Humans Telomerase reverse transcriptase HUMAN FORESKIN KERATINOCYTES E7 ONCOPROTEIN Cells Cultured Human papillomavirus types Genetics Messenger RNA Papillomavirus Infections Cancer EPITHELIAL-CELLS Oncogene Proteins Viral CERVICAL INTRAEPITHELIAL NEOPLASIA medicine.disease Cell Transformation Viral CANCER In vitro medicine.anatomical_structure Insect Science Cancer research Tumor Suppressor Protein p53 Erratum MESSENGER-RNA Differential (mathematics) |
| Zdroj: | Journal of Virology, 88(3), 1714-1724. American Society for Microbiology Schütze, D M, Snijders, P J F, ten Bosch, L, Kramer, D, Meijer, C J L M & Steenbergen, R D M 2014, ' Differential In Vitro Immortalization Capacity of Eleven, Probable High-Risk Human Papillomavirus Types ', Journal of Virology, vol. 88, no. 3, pp. 1714-1724 . https://doi.org/10.1128/JVI.02859-13 |
| ISSN: | 0022-538X |
| DOI: | 10.1128/JVI.02859-13 |
| Popis: | Epidemiological studies identified 12 high-risk HPV (hrHPV) types and 8 probable/possible hrHPV types that display different cancer risks. Functional studies on transforming properties of hrHPV are mainly limited to HPV16 and -18, which induce immortalization of human foreskin keratinocytes (HFKs) by successive bypass of two proliferative life span barriers, senescence and crisis. Here, we systematically compared the in vitro immortalization capacities, as well as influences on p53, pRb, hTERT, growth behavior, and differentiation capacity, of nine hrHPV types (HPV16, -18, -31, -33, -35, -45, -51, -52, and -59), and two probable hrHPV types (HPV66 and -70). By retroviral transduction, the respective E6/E7 coding sequences were expressed in HFKs from two or three independent donors. Reduced p53 levels and low-level hTERT expression in early-passage cells, as seen in HPV16-, -31-, -33-, and -35-, and to a lesser extent HPV18-transduced HFKs, was associated with continuous growth and an increased immortalization capacity. Less frequent immortalization by HPV45 and -51 and immortalization by HPV66 and -70 was preceded by an intervening period of strongly reduced growth (crisis) without prior increase in hTERT expression. Immortalization by HPV59 was also preceded by a period crisis, despite the onset of low hTERT expression at early passage. HPV52 triggered an extended life span but failed to induce immortality. Variations in p53 and pRb levels were not correlated with differences in alternative E6/E7 mRNA splicing in all hrHPV-transduced HFKs. On collagen rafts, transductants showed disturbed differentiation reminiscent of precancerous lesions. In conclusion, in vitro oncogenic capacities differ between the established hrHPV types, and both some established and probable hrHPV types display weak or moderate immortalization potential. |
| Databáze: | OpenAIRE |
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