SV40 large T-antigen

Endo, T. and Nidal-Ginard, B. (1988) SV40 large T antigen induces reentry of terminally differentiated myotubes into the cell cycle. In Kedes, L.H. and Stockdale, F.E. (eds) Cellular and Molecular Biology of Muscle Development. Alan R. Liss, New York, pp. 95-104. 

Figure 26.1 Immortalization of human cells Cells enter replicative senescence at mortality stage 1 (Ml Hayflick limit) after about 60 population doublings (PD). The protein p 16 accumulates in senescent cells. The simian virus 40 (SV40) large T antigen as well as the human papilloma virus (HPV) type 16-E6 and E7 proteins sequester the retinoblastoma protein (Rb) and/or p53 constitutively releases the transcription factor E2F. E2F induces expression proteins required for progression through Gl/S transition, thus the cells escape cell cycle arrest. At mortality stage 2 (M2), transformed cells must overcome senescence and crisis before they are immortalized. This is likely to involve the activation of telomerase either by the introduction of hTERT cDNA or by a genetic change that activates telomerase.

Takenouchi, T., Y. Iwamaru, M. Sato, T. Yokoyama, M. Shinagawa, and H. Kitani. 2007. Establishment and characterization of SV40 large T antigen-immortalized cell lines derived from fetal bovine brain tissues after prolonged cryopreservation. Cell Biolint 31(l) 57-64. 

Cheng, R. Z., M. A. Shammas, J. Li, and R. J. Shmookler Reis. 1997. Expression of SV40 large T antigen stimulates reversion of a chromosomal gene duplication in human cells. Exp Cell Res 234(2) 300-12. 

Schwartz, B., P. Vicart, C. Delouis, and D. Paulin. 1991. Mammalian cell lines can be efficiently established in vitro upon expression of the SV40 large T antigen driven by a promoter sequence derived from the human vimentin gene. Biol Cell 73(1) 7-14. 

Peterson, S. R., D. M. Gadbois, E. M. Bradbury, and P. M. Kraemer. 1995. Immortalization of human fibroblasts by SV40 large T antigen results in the reduction of cyclin D1 expression and subunit association with proliferating cell nuclear antigen and Wafl. Cancer Res 55(20) 4651-7. 

Primary cultured porcine or bovine brain capillary endothelial cells have been used as an in vitro model for the BBB. Recently, an immortalized cell line has been established from mouse, rat, and human brain capillary endothelial cells by infection with Simian virus 40 or transfection of SV40 large T antigen (45 -7). Tatsuta et al. established an immortalized mouse brain capillary endothelial cell line (MBEC4). The activity of y-glutamyl transpeptidase and alkaline phosphatase, specific marker enzymes for brain capillary endothelial cells, was half that in the brain capillary (45). Also, P-gp was expressed on the apical membrane of MBEC4 cells, which corresponds to the abluminal membrane of the brain... 

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