Holt S E, Wright W E, Shay J W
Department of Cell Biology and Neuroscience, University of Texas Southwestern Medical Center, Dallas 75235-9039, USA.
Eur J Cancer. 1997 Apr;33(5):761-6. doi: 10.1016/S0959-8049(97)00066-X.
The ends of vertebrate chromosome are composed of large tracts of a repeated sequence, TTAGGG, which are known as telomeres. Normal somatic cells progressively lose telomeric repeats with each successive cell division due to incomplete replication. Immortal and cancer cells compensate for telomeric loss by expressing the enzyme telomerase, an RNA-dependent DNA polymerase that maintains telomere length. Telomerase activity has been detected in almost 90% of all human cancers. Telomerase activity is generally absent in normal somatic tissues but is detected in adult testes, activated lymphocytes, and lower levels are expressed in proliferative cells of renewal tissues. Telomerase activity is downregulated in cells that exit the cell cycle via either terminal differentiation or (reversible) quiescence. Inhibition of telomerase activity in tumour cells may provide an effective way to treat cancer by potentially reducing the recurrence of tumours due to occult micro-metastases. An understanding of the pathways involved in telomerase regulation will be important for determining the most practical means of inhibiting its activity.
脊椎动物染色体的末端由大片重复序列TTAGGG组成，这些序列被称为端粒。由于复制不完全，正常体细胞在每次连续细胞分裂时都会逐渐丢失端粒重复序列。永生细胞和癌细胞通过表达端粒酶来补偿端粒的丢失，端粒酶是一种依赖RNA的DNA聚合酶，可维持端粒长度。在几乎90%的人类癌症中都检测到了端粒酶活性。端粒酶活性在正常体细胞组织中通常不存在，但在成年睾丸、活化的淋巴细胞中可检测到，并且在更新组织的增殖细胞中表达水平较低。通过终末分化或（可逆的）静止状态退出细胞周期的细胞中端粒酶活性下调。抑制肿瘤细胞中的端粒酶活性可能为治疗癌症提供一种有效方法，因为这可能会减少由于隐匿性微转移导致的肿瘤复发。了解端粒酶调控所涉及的途径对于确定抑制其活性的最实用方法将具有重要意义。
