Shay J W, Wright W E
Department of Cell Biology and Neuroscience, University of Texas Southwestern Medical Center, Dallas 75235-9039, USA.
Curr Opin Oncol. 1996 Jan;8(1):66-71. doi: 10.1097/00001622-199601000-00012.
The chromosome ends are specialized nucleoprotein structures called telomeres, which are essential for stable chromosome maintenance. In tumor-derived cell lines telomeres are maintained by the ribonucleoprotein enzyme telomerase. Telomerase activity is repressed in almost all normal human somatic cells. Due to the end replication problem, progressive telomere shortening occurs in normal somatic cells, leading to a limited replicative capacity and eventually resulting in cellular senescence. In the presence of viral oncogenes or some somatic mutations that block cellular senescence, cells continue to divide and telomere erosion continues. This continuing telomere erosion ultimately leads to the activation of telomerase, a necessary event for the sustained growth of most human tumors.
染色体末端是被称为端粒的特殊核蛋白结构，对于稳定的染色体维持至关重要。在肿瘤衍生的细胞系中，端粒由核糖核蛋白酶端粒酶维持。端粒酶活性在几乎所有正常人类体细胞中受到抑制。由于末端复制问题，正常体细胞中会发生渐进性端粒缩短，导致复制能力受限并最终导致细胞衰老。在存在病毒癌基因或一些阻断细胞衰老的体细胞突变的情况下，细胞继续分裂且端粒侵蚀持续。这种持续的端粒侵蚀最终导致端粒酶激活，这是大多数人类肿瘤持续生长的必要事件。
