[Mechanism of cell proliferation--cell cycle, oncogenes, and senescence].
[Mechanism of cell proliferation--cell cycle, oncogenes, and senescence].
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[细胞增殖机制——细胞周期、癌基因和衰老]。
DOI：
10.1002/chin.200714268
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
T. Ide
中科院分区：
文献类型：
--
作者：
T. Ide
细胞增殖通过G 0期和细胞周期之间的转变来调节。我们分离了一个哺乳动物温度敏感性突变细胞系，该细胞系在从G 0期到细胞周期的功能上有缺陷。衰老的人体细胞在任何生长因子的刺激下都不能从G 0期进入细胞周期。端粒缩短是细胞衰老的原因之一，端粒酶的重新表达使人的体细胞永生化。永生化的人体细胞具有正常的表型，不仅可用于基础研究，而且可用于临床和应用领域。p53和p21的激活/诱导在从端粒缩短到生长停滞的信号转导过程中的重要性现已被广泛接受，但其确切机制尚不清楚。我们发现MAP激酶级联和组蛋白乙酰化酶在表达p21的信号传导过程中具有重要作用。肿瘤组织和细胞具有很强的端粒酶活性，而大多数正常人体组织显示很弱或无活性。端粒酶活性是一个很好的早期肿瘤诊断的标志物，因为在非常早期的肿瘤，甚至在一些癌前组织中检测到显着的端粒酶活性与癌旁正常组织相比。端粒/端粒酶是癌症化学治疗的候选靶标，并且发现废除端粒功能的试剂通过诱导凋亡有效地杀死肿瘤细胞，而它对正常细胞的活力没有影响。
Cell proliferation is regulated through a transition between the G0 phase and cell cycle. We isolated a mammalian temperature-sensitive mutant cell line defective in the function from the G0 phase to cell cycle. Senescent human somatic cells fail to enter into the cell cycle from the G0 phase with stimulation by any growth factor. Telomere shortening was found to be a cause of cellular senescence, and reexpression of telomerase immortalized human somatic cells. Immortalized human somatic cells showed normal phenotypes and were useful not only for basic research but also for clinical and applied fields. The importance of p53 and p21 activation/induction i now well accepted in the signal transduction process from telomere shortening to growth arrest, but the precise mechanism is largely unknown as yet. We found that the MAP kinase cascade and histone acetylase have an important role in the signaling process to express p21. Tumor tissues and cells were found to have strong telomerase activity, while most normal somatic human tissues showed very weak or no activity. Telomerase activity was shown to be a good marker for early tumor diagnosis because significant telomerase activity was detected in very early tumors or even in some precancerous tissues compared with adjacent normal tissues. Telomere/telomerase is a candidate target for cancer chemotherapeutics, and an agent that abrogated telomere functions was found to kill tumor cells effectively by inducing apoptosis whereas it showed no effect on the viability of normal cells.