Simian Virus 40 Small Tumor Antigen Activates AKT and Telomerase and Induces Anchorage-Independent Growth of Human Epithelial Cells
Autor: | Richard Schlegel, Tim Veldman, Hang Yuan, Kathleen Rundell |
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Rok vydání: | 2002 |
Předmět: |
Keratinocytes
Telomerase Cell Survival Antigens Polyomavirus Transforming Immunology Simian virus 40 Protein Serine-Threonine Kinases Biology Microbiology Transformation and Oncogenesis 3T3 cells Mice Antigen Proto-Oncogene Proteins Virology Cell Adhesion medicine Animals Humans Telomerase reverse transcriptase Phosphorylation Protein kinase B Cells Cultured 3T3 Cells Transfection Molecular biology DNA-Binding Proteins Enzyme Activation medicine.anatomical_structure Insect Science Keratinocyte Proto-Oncogene Proteins c-akt Cell Division |
Zdroj: | Journal of Virology. 76:10685-10691 |
ISSN: | 1098-5514 0022-538X |
Popis: | Human keratinocytes immortalized by full-length or early-region simian virus 40 (SV40) DNA grow in agarose and form tumors in nude mice, in contrast to keratinocytes immortalized by the E6/E7 genes of human papillomaviruses. To determine the molecular basis for this biological difference in growth, we have used the individual SV40 oncogenes (large T antigen [LT] and small t antigen [st]) and human papillomavirus oncogenes (E6/E7) to study the progression of human epithelial cells from the nonimmortal to the immortal state as well as from the immortal to the anchorage-independent state. Transfection of primary human foreskin keratinocytes with LT did not immortalize cells but did extend the in vitro life span and produced cells that were resistant to calcium- and serum-induced terminal differentiation. Cells transfected with st alone did not passage beyond vector-transfected keratinocytes. The simultaneous expression of LT- and st-immortalized keratinocytes occurred without evidence of crisis and, as anticipated, these immortal cells were anchorage- independent for growth. Interestingly, we found that keratinocytes expressing both LT and st, but not keratinocytes with LT alone, exhibited increased phosphorylation of the protein kinase AKT. In addition, AKT activation was paralleled by an increase in telomerase activity. Addition of st to anchorage-dependent keratinocytes, expressing either LT (nonimmortal) or E6/E7 (immortal), converted the cells to anchorage independence, with similar accompanying increases in AKT phosphorylation and telomerase activity. However, it was not possible to induce keratinocyte growth in agarose with activated AKT and/or overexpressed hTERT, indicating that these newly defined st-induced activities are not sufficient for progression to the anchorage-independent state. |
Databáze: | OpenAIRE |
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