Telomeric recombination in mismatch repair deficient human colon cancer cells after telomerase inhibition
Telomeric recombination in mismatch repair deficient human colon cancer cells after telomerase inhibition
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DOI：
10.1158/0008-5472.can-04-0323
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发表时间：
2004-05-15
期刊：
影响因子：
11.2
通讯作者：
Shay, JW
中科院分区：
文献类型：
--
作者：
Bechter, OE;Zou, Y;Shay, JW
大多数人类恶性肿瘤使用端粒酶来维持端粒稳态。因此，抗端粒酶疗法是一种有前途的癌症特异性疗法。端粒选择性延长途径 (ALT) 是一种基于重组、不依赖于端粒酶的端粒长度控制机制。人们普遍认为，当癌细胞逃脱端粒酶抑制时，ALT 就会发挥作用。然而，没有报告支持这种治疗抵抗的概念。我们抑制了具有错配修复缺陷的人类癌细胞系中的端粒酶，并观察到不依赖端粒酶的、类似 ALT 的端粒伸长。这是当端粒酶被抑制时在人类癌细胞中诱导不依赖端粒酶的端粒延长的第一份报告，从而描述了抗端粒酶治疗的新耐药机制。
The majority of human malignancies use telomerase to maintain telomere homeostasis. Antitelomerase therapy is therefore a promising approach for a cancer-specific therapy. The alternative lengthening of telomeres pathway (ALT) is a recombination-based, telomerase-independent mechanism of telomere length control. It is widely believed that ALT could be engaged when cancer cells escape from telomerase inhibition. However, no reports exist that would support this concept of therapy resistance. We inhibited telomerase in a human cancer cell line with a mismatch repair defect and observed a telomerase-independent, ALT-like telomere elongation. This is the first report of inducing a telomerase-independent telomere elongation in human cancer cells when telomerase is inhibited, thus describing a novel mechanism of resistance to antitelomerase therapy.