LOSS OF T-ANTIGEN SEQUENCES ALLOWS SV40-TRANSFORMED HUMAN-CELLS IN CRISIS TO ACQUIRE A SENESCENT-LIKE PHENOTYPE

Normal human cells transfected with SV40 DNA exhibit an extended proli ferative potential compared with controls, but they eventually enter a phase known as ''crisis.'' During crisis, extensive cell death occurs and the cells exhibit some gene expression changes similar to senesce nt cells. This article presents results which indicate that crisis mos t likely depends on expression of the viral gene T-antigen. We have ob tained a unique subpopulation of cells that have deleted the T-antigen gene and, rather than dying as cells do in crisis, remain viable and exhibit some senescent-like characteristics. We also found that the SV 40 promoter is poorly expressed in senescent versus young cells. We hy pothesize that decreased activity of the viral promoter may result in decreased expression of T-antigen, which is challenged by over-express ion of the cell cycle inhibitors such as p21(Sdil). Conflicting signal s to proceed/halt cell cycle progression result in the cell death asso ciated with crisis.