Chen W, Chen S M, Yu Y, Xiao B K, Huang Z W, Tao Z Z
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, China.
J Laryngol Otol. 2010 Jul;124(7):778-83. doi: 10.1017/S0022215109992854. Epub 2010 Apr 20.
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.
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.
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.
在癌细胞的整个进展和增殖过程中，端粒长度必须得以维持。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一个靶点。然而，一些癌细胞通过一种称为“端粒替代延长”的替代机制维持端粒长度。为了确定端粒酶抑制与端粒替代延长途径的启动之间的关系，我们研究了端粒酶活性降低和未降低的Hep-2细胞中的端粒酶活性及端粒维持情况。
我们研究了正常Hep-2细胞系以及端粒酶抑制处理后残留细胞中的端粒酶活性水平。此外，我们寻找端粒替代延长机制的标志物蛋白的表达情况。
在残留细胞中，端粒酶活性被消除。然而，这些细胞中端粒替代延长生物标志物的水平较高，这表明在端粒酶抑制后存在一种维持端粒的替代机制。这些结果可能对新癌症治疗方案的设计产生重大影响。
