Dhaene K, Van Marck E, Parwaresch R
Laboratory of Pathology, University of Antwerp, Belgium.
Virchows Arch. 2000 Jul;437(1):1-16. doi: 10.1007/s004280000189.
In the mid 1990s, the hypothesis emerged that the upregulation or re-expression of a telomere-synthesising ribonucleoprotein, called telomerase, is a critical event responsible for continuous tumour cell growth. In contrast to normal cells, in which gradual mitosis-related erosion of telomeres eventually limits replicative life span, tumour cells have telomerase and show no loss of these chromosomal ends. These data suggest that telomere stabilisation may be required for cells to escape replicative senescence and to proliferate indefinitely. Because of the close association between telomerase and malignancy, both pathologists and clinicians expect this molecule to be a useful malignancy-marker and a new therapeutic target. This review focuses on the components of the human telomere and of the human telomerase enzyme. A synopsis of reports studying the clinical-diagnostic value of telomere length measurements, of telomerase activity analyses and of the in situ telomerase detection is given. Finally, a summary of recent experimental work that sheds new light on the biological role of this fascinating molecule is presented.
20世纪90年代中期，有假说认为，一种名为端粒酶的端粒合成核糖核蛋白的上调或重新表达是肿瘤细胞持续生长的关键事件。与正常细胞不同，正常细胞中端粒与有丝分裂相关的逐渐侵蚀最终会限制其复制寿命，而肿瘤细胞具有端粒酶，且这些染色体末端不会丢失。这些数据表明，端粒稳定可能是细胞逃避复制性衰老并无限增殖所必需的。由于端粒酶与恶性肿瘤密切相关，病理学家和临床医生都期望这种分子成为一种有用的恶性肿瘤标志物和新的治疗靶点。本综述重点关注人类端粒和人类端粒酶的组成部分。概述了研究端粒长度测量、端粒酶活性分析及端粒酶原位检测的临床诊断价值的报告。最后，总结了最近的实验工作，这些工作为这个迷人分子的生物学作用提供了新的线索。
