Karyotype instability and anchorage-independent growth in telomerase-immortalized fibroblasts from two centenarian individuals
Karyotype instability and anchorage-independent growth in telomerase-immortalized fibroblasts from two centenarian individuals
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DOI：
10.1016/s0006-291x(03)01484-0
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发表时间：
2003-09-05
影响因子：
3.1
通讯作者：
Nuzzo, F
中科院分区：
文献类型：
--
作者：
Mondello, C;Chiesa, M;Nuzzo, F
一些报道表明，人端粒酶催化亚单位基因（hTERT）的异位表达导致体外培养的人成纤维细胞的寿命无限期延长，而不出现癌症相关的变化。我们用含hTERT的逆转录病毒感染了两种来自百岁老人的成纤维细胞株，并分离了大量转导的人群（cen2tel和cen3tel）。在这两个群体中，hTERT表达重建端粒酶活性并延长寿命。在cen2tel中，观察到净端粒延长，而在cen3tel中，端粒稳定在低于衰老亲本细胞中检测到的长度。有趣的是，cen2tel和cen3tel细胞都发生了染色体异常，首先是数量异常，然后是结构异常。此外，cen3tel细胞获得了在没有固体支持物的情况下生长的能力，这是转化细胞的典型特征。我们在这里提出的结果突出了一个意想不到的可能结果的细胞永生化驱动的端粒酶再激活，并表明，在某些情况下，细胞复制能力的人工扩展可以增加发生基因组改变的概率，这可能导致细胞转化。(C)2003年由Elsevier Inc.出版
Several reports have shown that the ectopic expression of the human telomerase catalytic subunit gene (hTERT) leads to an indefinite extension of the life span of human fibroblasts cultured in vitro without the appearance of cancer-associated changes. We infected two fibroblast strains derived from centenarian individuals with an hTERT containing retrovirus and isolated transduced massive populations (cen2tel and cen3tel). In both populations, hTERT expression reconstituted telomerase activity and extended the life span. In cen2tel, a net telomere lengthening was observed while, in cen3tel, telomeres stabilized at a length lower than that detected in senescent parental cells. Interestingly, both cen2tel and cen3tel cells developed chromosome anomalies, numerical first and structural thereafter. Moreover, cen3tel cells acquired the ability to grow in the absence of solid support, a typical feature of transformed cells. The results we present here highlight an unexpected possible outcome of cellular immortalization driven by telomerase reactivation, and indicate that, in some cases, an artificial extension of cellular replicative capacity can increase the probability of occurrence of genomic alterations, which can lead to cellular transformation. (C) 2003 Published by Elsevier Inc.