TELOMERE ELONGATION IN IMMORTAL HUMAN-CELLS WITHOUT DETECTABLE TELOMERASE ACTIVITY
TELOMERE ELONGATION IN IMMORTAL HUMAN-CELLS WITHOUT DETECTABLE TELOMERASE ACTIVITY
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DOI：
10.1002/j.1460-2075.1995.tb00098.x
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发表时间：
1995-09-01
期刊：
影响因子：
11.4
通讯作者：
REDDEL, RR
中科院分区：
文献类型：
--
作者：
BRYAN, TM;ENGLEZOU, A;REDDEL, RR
人类细胞的永生化通常与端粒酶的再活化有关，端粒酶是一种核糖核蛋白酶，它将TTAGGG重复序列添加到端粒上并补偿其缩短。所有正常人成纤维细胞端粒酶活性均为阴性，13个DNA肿瘤病毒转化的细胞培养物在危机前（即非永生化）阶段也为阴性。35个永生化细胞系中，20个具有预期的端粒酶活性，但15个没有检测到端粒酶。15个端粒酶阴性的永生化细胞系均具有长达50 kb的长而不均一的端粒，端粒酶阴性和端粒酶阳性细胞之间的杂交细胞衰老。两个衰老的杂交细胞表现出端粒酶活性，表明端粒酶的激活不足以永生化。一些杂交克隆随后重新开始增殖，并成为永生化的，无论有或没有端粒酶活性，那些没有端粒酶活性也有很长的和异质性的端粒。总之，这些数据表明，存在延长或稳定的端粒是必要的永生化，这可能是通过重新激活端粒酶或通过一种新的和尚未确定的机制。
Immortalization of human cells is often associated with reactivation of telomerase, a ribonucleoprotein enzyme that adds TTAGGG repeats onto telomeres and compensates for their shortening. We examined whether telomerase activation is necessary for immortalization, All normal human fibroblasts tested were negative for telomerase activity, Thirteen out of 13 DNA tumor virus-transformed cell cultures were also negative in the pre-crisis (i.e. non-immortalized) stage, Of 35 immortalized cell lines, 20 had telomerase activity as expected, but 15 had no detectable telomerase. The 15 telomerase-negative immortalized cell lines all had very long and heterogeneous telomeres of up to 50 kb, Hybrids between telomerase-negative and telomerase-positive cells senesced. Two senescent hybrids demonstrated telomerase activity, indicating that activation of telomerase is not sufficient for immortalization. Some hybrid clones subsequently recommenced proliferation and became immortalized either with or without telomerase activity, Those without telomerase activity also had very long and heterogeneous telomeres. Taken together, these data suggest that the presence of lengthened or stabilized telomeres is necessary for immortalization, and that this may be achieved either by the reactivation of telomerase or by a novel and as yet unidentified mechanism.