Rubelj I, Venable S F, Lednicky J, Butel J S, Bilyeu T, Darlington G, Surmacz E, Campisi J, Pereira-Smith O M
Roy M. and Phyllis Gough Huffington Center on Aging, Baylor College of Medicine, Houston, Texas, USA.
J Gerontol A Biol Sci Med Sci. 1997 Sep;52(5):B229-34. doi: 10.1093/gerona/52a.5.b229.
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.
与对照相比，用SV40 DNA转染的正常人类细胞表现出延长的增殖潜能，但它们最终会进入一个被称为“危机”的阶段。在危机期间，会发生广泛的细胞死亡，并且细胞表现出一些与衰老细胞相似的基因表达变化。本文呈现的结果表明，危机很可能依赖于病毒基因T抗原的表达。我们获得了一个独特的细胞亚群，这些细胞缺失了T抗原基因，并且不像处于危机中的细胞那样死亡，而是保持存活并表现出一些衰老样特征。我们还发现，与年轻细胞相比，SV40启动子在衰老细胞中表达较差。我们推测，病毒启动子活性降低可能导致T抗原表达减少，而细胞周期抑制剂如p21Sdi1的过表达对其构成挑战。细胞周期进展的进行/停止信号相互冲突，导致了与危机相关的细胞死亡。
