Artandi S E, DePinho R A
Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Curr Opin Genet Dev. 2000 Feb;10(1):39-46. doi: 10.1016/s0959-437x(99)00047-7.
Progressive telomere shortening occurs with the division of primary human cells and activates tumor suppressor pathways, triggering senescence and inhibiting tumorigenesis. Loss of p53 function, however, allows continued cell division despite increasing telomere dysfunction and entry into telomere crisis. Recent data suggest that the severe chromosomal instability of telomere crisis promotes secondary genetic changes that facilitate carcinogenesis. Reactivation of telomerase stabilizes telomere ends and allows continued tumor growth.
随着原代人类细胞的分裂，端粒会逐渐缩短，并激活肿瘤抑制途径，引发细胞衰老并抑制肿瘤发生。然而，p53功能的丧失会使细胞尽管端粒功能障碍加剧并进入端粒危机仍能继续分裂。最近的数据表明，端粒危机时严重的染色体不稳定性会促进继发性基因变化，从而促进癌症发生。端粒酶的重新激活可稳定端粒末端并使肿瘤持续生长。
