端粒在基因组稳定、细胞核结构以及减数分裂中染色体配对中发挥关键作用。细胞每分裂一次,端粒会缩短,缩短的端粒可能再延长或不延长,这取决于细胞内是否存在一种专用酶-端粒酶。由于人体的多数体细胞并不表达端粒酶,因此发育和衰老过程中端粒必然缩短。在生理条件下,端粒缩短与延长的细胞增殖相矛盾,因此端粒长度决定了细胞的增殖潜能,并作为细胞无限生长的预防机制。相反,在细胞增殖检查点受破坏的细胞中,缩短的端粒可导致染色体融合并启动断裂-融合-桥周期,这极大地促发了基因组不稳定。在体外研究中,转化细胞中由于端粒严重缩短造成的基因组高度不稳定,在这种细胞种蓄积了有害的遗传改变,从而导致细胞最终死亡(危象)。同时,随机的遗传或拟遗传学改变可使细胞获得端粒维持机制(以及其它肿瘤表型),从而成为永生细胞。在体内研究中,尽管在早期肿瘤细胞中发现端粒缩短和其它形式的端粒功能障碍可能使基因组不稳定,但端粒功能障碍对于人类肿瘤表型的直接作用有待进一步研究。 Telomeres play key roles in genome stabilization, nuclear structure, and chromosome pairing in meiosis. Each division of the cells, the telomeres will shorten and the shortened telomeres may or may not be lengthened, depending on whether a specific enzyme, telomerase, is present in the cell. Since most human somatic cells do not express telomerase, telomeres are inevitably shortened during development and aging. Under physiological conditions, telomere shortening is incompatible with prolonged cell proliferation, so telomere length determines the cell’s proliferative potential and serves as a preventative mechanism for unlimited cell growth. In contrast, shortened telomeres can lead to chromosomal fusion and initiate the break-thaw-bridge cycle in cells that have been damaged at the point of cell proliferation check, which greatly contributes to genomic instability. In in vitro studies, the genomic instability in transformed cells due to severe telomere shortening accumulates harmful genetic changes in this cell species, resulting in the eventual cell death (crisis). In the meantime, random genetic or quasi-genetic changes allow cells to acquire telomere maintenance mechanisms (as well as other tumor phenotypes) and become immortalized cells. In vivo studies, although the telomere shortening and other forms of telomere dysfunction found in early tumor cells may destabilize the genome, the direct role of telomere dysfunction in human tumor phenotype remains to be further studied.