SV40-mediated transformation and immortalization of human cells.
SV40 infection of human cells results in both transformation and lytic infection. We have used origin-defective viral mutants which are unable to replicate in permissive cells to help analysis of transformation. Expression of large T antigen (T ag) and small t antigen results in the altered growth phenotypes characteristic of transformation in other species. Human diploid fibroblasts (HF) have a limited lifespan and undergo senescence; T ag results in extension of lifespan but only in rare cases are the cells capable of continuous growth and are immortal. We have developed matched sets of non-immortal and immortal transformed HF for assessment of the steps required for immortalization. Results are summarized to characterize both T-dependent and T-independent functions. A novel growth suppressor gene SEN6 has been identified, the inactivation of which is required for immortalization; it may also serve as a marker to distinguish cells in which SV40 is replicating from those in which it is responsible for tumorigenesis.
Department of Microbiology and Molecular Genetics UMD-New Jersey Medical School, Newark 07103-2714, USA.
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D016475:3T3 Cells; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D013539:Simian virus 40 / Q000472:pathogenicity*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014412:Tumor Virus Infections / Q000473:pathology*
D000952:Antigens, Polyomavirus Transforming; D016159:Tumor Suppressor Protein p53