Loss of T-antigen sequences allows SV40-transformed human cells in crisis to acquire a senescent-like phenotype

Abstract

Normal human cells transfected with SV40 DNA exhibit an extended proliferative 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 senescent cells. This article presents results which indicate that crisis most likely depends on expression of the viral gene T-antigen. We have obtained 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 SV40 promoter is poorly expressed in senescent versus young cells. We hypothesize that decreased activity of the viral promoter may result in decreased expression of T-antigen, which is challenged by over-expression of the cell cycle inhibitors such as p21(SB1). Conflicting signals to proceed/halt cell cycle progression result in the cell death associated with crisis.