Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol 52, Issue 5 B229-B234, Copyright © 1997 by The Gerontological Society of America
Loss of T-antigen sequences allows SV40-transformed human cells in crisis to acquire a senescent-like phenotype
I Rubelj, SF Venable, J Lednicky, JS Butel, T Bilyeu, G Darlington, E Surmacz, J Campisi and OM Pereira-Smith
Roy M. and Phyllis Gough Huffington Center on Aging, Baylor College of Medicine, Houston, Texas, USA.
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 p21Sdi1. Conflicting signals to proceed/halt cells cycle
progression result in the cell death associated with crisis.
