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首页> 外文期刊>Molecular and Cellular Biology >Rat embryo fibroblasts immortalized with simian virus 40 large T antigen undergo senescence upon its inactivation.
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Rat embryo fibroblasts immortalized with simian virus 40 large T antigen undergo senescence upon its inactivation.

机译：猿猴病毒40大T抗原永生的大鼠胚胎成纤维细胞在灭活后会衰老。

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Introduction of simian virus 40 T antigen into rodent fibroblasts gives rise to cells that can proliferate indefinitely but are dependent upon it for maintenance of their growth once the normal mitotic life span has elapsed. Inactivation of T antigen in these immortalized cells causes rapid and irreversible cessation of growth. To determine whether this growth arrest is associated with entry into senescence, we have undertaken a genetic and biological analysis of conditionally immortal (tsa) cell lines derived by immortalizing rat embryo fibroblasts with the thermolabile tsA58 T antigen. This analysis has identified the following parallels between the tsa cells after inactivation of T antigen and senescent rat embryo fibroblasts: (i) growth arrest is irreversible; (ii) it occurs in G1 as well as G2; (iii) the G1 block can be partially overcome by stimulation with 20% fetal calf serum, but the G2 block cannot be overcome; (iv) 20% fetal calf serum induces c-fos, but c-myc is unaltered; and (v) fibronectin and p21(Waf1/Cip1/Sdi1) are upregulated upon growth arrest. These results suggest that T-antigen-immortalized fibroblasts are committed to undergo senescence but are prevented from undergoing this process by T antigen. Inactivation of T antigen removes this block and results in senescence of the cells. Thus, these cell lines may represent a powerful system for study of the molecular basis of entry into senescence.
机译：将猿猴病毒40 T抗原引入啮齿动物的成纤维细胞中会产生可以无限增殖的细胞，但是一旦正常的有丝分裂寿命结束，就需要依靠它来维持其生长。这些永生化细胞中T抗原的失活会导致生长迅速且不可逆转地停止。为了确定这种生长停滞是否与衰老有关，我们对通过使用不耐热的tsA58 T抗原使大鼠胚胎成纤维细胞永生化而产生的有条件永生（tsa）细胞系进行了遗传和生物学分析。该分析已鉴定出T抗原失活后tsa细胞与衰老大鼠胚胎成纤维细胞之间存在以下相似之处：（i）生长停滞是不可逆的; （ii）它出现在G1和G2中; （iii）用20％的胎牛血清刺激可以部分克服G1阻滞，但不能克服G2阻滞; （iv）20％的胎牛血清可诱导c-fos，但c-myc不变; （v）纤连蛋白和p21（Waf1 / Cip1 / Sdi1）在生长停滞时被上调。这些结果表明，T抗原永生化的成纤维细胞致力于衰老，但是被T抗原阻止其经历该过程。 T抗原的失活去除了该阻滞并导致细胞衰老。因此，这些细胞系可能是研究衰老的分子基础的强大系统。

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