Urquidi V, Tarin D, Goodison S
Cancer Center, University of California, San Diego, La Jolla 92093-0684, USA.
Ann Med. 1998 Oct;30(5):419-30. doi: 10.3109/07853899809002483.
The biology of telomeres and telomerase has been the subject of intensive investigative effort since it became evident that they play a significant role in two important biological processes, the loss of cellular replicative capacity inherent to organismal ageing and the unrestricted cell proliferation characteristic of carcinogenesis. Telomere shortening in normal cells is a result of DNA replication events, and reduction beyond a critical length is a signal for cellular senescence. One of the cellular mechanisms used to overcome proliferative restriction is the activation of the enzyme telomerase, which replaces the loss of telomeric DNA that occurs at each cell division. Studies have demonstrated that tumours have shorter telomeres than normal tissue and that telomerase is activated in up to 90% of all human cancers while it is present only in a limited range of normal adult tissues. The role of telomerase in the extension of the cellular replicative lifespan has recently been shown by ectopic expression of the enzyme, being consistent with the oncogenesis model whereby the acquisition of an 'immortal' phenotype is a requirement for advanced tumour progression. In this article we review the present knowledge of telomeres and telomerase in cancer and discuss the potential use of this enzyme as a diagnostic and prognostic tumour marker and as a target for cancer therapy.
自端粒和端粒酶在两个重要生物学过程中发挥重要作用变得明显以来，它们的生物学特性一直是深入研究的对象，这两个过程分别是生物体衰老所固有的细胞复制能力丧失以及癌症发生所特有的不受限制的细胞增殖。正常细胞中端粒缩短是DNA复制事件的结果，缩短超过临界长度是细胞衰老的信号。用于克服增殖限制的细胞机制之一是激活端粒酶，端粒酶可替代每次细胞分裂时发生的端粒DNA丢失。研究表明，肿瘤的端粒比正常组织短，并且在所有人类癌症中，高达90%的癌症中端粒酶被激活，而端粒酶仅存在于有限范围的正常成人组织中。最近通过该酶的异位表达表明了端粒酶在延长细胞复制寿命中的作用，这与肿瘤发生模型一致，即获得“永生”表型是晚期肿瘤进展的必要条件。在本文中，我们综述了目前关于癌症中端粒和端粒酶的知识，并讨论了该酶作为诊断和预后肿瘤标志物以及癌症治疗靶点的潜在用途。
