SV40-induced immortalization of human cells.
For several decades simian virus 40 (SV40) early region genes have been used as a means of generating immortalized human cell lines; however, the molecular mechanisms of this process have begun to be understood only recently. SV40-induced immortalization proceeds via two phases. In the first phase ("lifespan extension"), cells continue proliferating for a limited number of population doublings beyond the point at which normal cells undergo senescence. This is mainly due to the ability of SV40 large T antigen (LTAg) to bind to the protein products of the p53 and retinoblastoma (Rb) genes. The second phase ("immortalization") occurs in only a small minority of cells, and cell hybridization analyses indicate that this is a gene inactivation event. The gene or genes involved are currently unknown, but chromosomal localization data are accumulating which should make their cloning and characterization possible in the near future.
Bryan
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TM
Children's Medical Research Institute, Sydney, NSW, Australia.
Reddel
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RR
D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D016922:Cellular Senescence; D006801:Humans; D013539:Simian virus 40 / Q000235:genetics*; D016615:Telomere