Satyanarayana Ande, Manns Michael P, Rudolph K Lenhard
Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, Hannover, Germany.
Hepatology. 2004 Aug;40(2):276-83. doi: 10.1002/hep.20308.
Telomere shortening limits the proliferative capacity of primary human cells and restrains the regenerative capacity of organ systems during chronic diseases and aging. Telomere shortening apparently has a dual role in tumor development and progression. On the one hand, it induces chromosomal instability and the initiation of cancer; on the other hand, tumor progression requires stabilization of telomeres. The predominant mechanism of telomere stabilization in tumor cells is the activation of the telomere-synthesizing enzyme telomerase. The potential use of telomerase activators for the treatment of regenerative disorders will ultimately depend on their effects on tumorigenesis. This review focuses on the role of telomere shortening and telomerase in carcinogenesis with a special focus on hepatocellular carcinoma.
端粒缩短限制了原代人细胞的增殖能力,并在慢性疾病和衰老过程中抑制器官系统的再生能力。端粒缩短在肿瘤发生和发展过程中显然具有双重作用。一方面,它诱导染色体不稳定和癌症的起始;另一方面,肿瘤进展需要端粒的稳定。肿瘤细胞中端粒稳定的主要机制是端粒合成酶端粒酶的激活。端粒酶激活剂用于治疗再生障碍的潜在用途最终将取决于它们对肿瘤发生的影响。本综述重点关注端粒缩短和端粒酶在致癌作用中的作用,特别关注肝细胞癌。