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Critical Reviews™ in Oncogenesis
SJR: 0.946 SNIP: 0.503 CiteScore™: 2

ISSN Print: 0893-9675
ISSN Online: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.v5.i4.10
pages 331-357

SV40-lnduced Immortalization of Human Cells

Tracy Bryan
Children's Medical Research Institute
Roger R. Redder
Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, Sydney, NSW 2145, Australia


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.

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