Telomerase inhibition alters telomere maintenance mechanisms in laryngeal squamous carcinoma cells
Telomerase inhibition alters telomere maintenance mechanisms in laryngeal squamous carcinoma cells
复制标题
端粒酶抑制改变喉鳞状细胞癌细胞的端粒维持机制
DOI：
10.1017/s0022215109992854
复制
发表时间：
2010-07-01
影响因子：
1.7
通讯作者：
Tao, Z. Z.
中科院分区：
文献类型：
--
作者：
Chen, W.;Chen, S. M.;Tao, Z. Z.
背景和目的：端粒长度必须维持在整个癌细胞的进展和增殖。在大多数肿瘤中，端粒酶活性维持端粒长度。因此，端粒酶是癌症治疗的靶点。然而，一些癌细胞通过另一种被称为“端粒的选择性延长”的机制来维持端粒长度。为了确定端粒酶抑制如何与端粒选择性延长途径的启动有关，我们研究了端粒酶活性降低和端粒活性不降低的Hep-2细胞的端粒酶活性和端粒维持。材料和方法：我们研究了正常Hep-2细胞系和端粒酶抑制后残留细胞的端粒酶活性水平。此外，我们寻找了端粒延长机制的标记蛋白的表达。结果与结论：残余细胞端粒酶活性消失。然而，这些细胞具有更高水平的端粒选择性延长生物标志物，提示端粒酶抑制后端粒维持的另一种机制。这些结果可能会对设计新的癌症治疗方法产生重大影响。
Abstract Background and purpose: Telomere length must be maintained throughout cancer cell progression and proliferation. In most tumours, telomerase activity maintains telomere length. Therefore, telomerase is a target for cancer treatments. However, some cancer cells maintain telomere length through an alternative mechanism termed ‘alternative lengthening of telomeres’. To determine how telomerase inhibition relates to the initiation of the alternative lengthening of telomeres pathway, we investigated telomerase activity and telomere maintenance in Hep-2 cells with and without reduced telomerase activity. Materials and methods: We investigated telomerase activity levels in a normal Hep-2 cell line and in residual cells following telomerase inhibition treatment. Additionally, we looked for expression of a marker protein for the alternative lengthening of telomeres mechanism. Results and conclusions: In the residual cells, telomerase activity was eliminated. However, these cells had higher levels of the alternative lengthening of telomeres biomarker, suggesting an alternative mechanism for telomere maintenance following telomerase inhibition. These results could have a major impact on the design of new cancer treatments.