Nakayama J, Tahara H, Tahara E, Saito M, Ito K, Nakamura H, Nakanishi T, Tahara E, Ide T, Ishikawa F
Department of Life Science, Tokyo Institute of Technology, Yokohama, Japan.
Nat Genet. 1998 Jan;18(1):65-8. doi: 10.1038/ng0198-65.
Telomerase is a specialized type of reverse transcriptase which catalyzes the synthesis and extension of telomeric DNA (for review, see ref.1). This enzyme is highly active in most cancer cells, but is inactive in most somatic cells. This striking observation led to the suggestion that telomerase might be important for the continued growth or progression of cancer cells. However, little is known about the molecular mechanism of telomerase activation in cancer cells. Human telomerase reverse transcriptase (hTRT) has recently been identified as a putative human telomerase catalytic subunit. We transfected the gene encoding hTRT into telomerase-negative human normal fibroblast cells and demonstrated that expression of wild-type hTRT induces telomerase activity, whereas hTRT mutants containing mutations in regions conserved among other reverse transcriptases did not. Hepatocellular carcinoma (20 samples) and non-cancerous liver tissues (19 samples) were examined for telomerase activity and expression of hTRT, the human telomerase RNA component (hTR; encoded by TERC) and the human telomerase-associated protein (hTLP1; encoded by TEP1). A significant correlation between hTRT expression and telomerase activity was observed. These results indicate that the hTRT protein is the catalytic subunit of human telomerase, and that it plays a key role in the activation of telomerase in cancer cells.
端粒酶是一种特殊类型的逆转录酶，可催化端粒DNA的合成与延伸（综述见参考文献1）。这种酶在大多数癌细胞中高度活跃，但在大多数体细胞中无活性。这一显著现象提示端粒酶可能对癌细胞的持续生长或进展至关重要。然而，关于癌细胞中端粒酶激活的分子机制知之甚少。人端粒酶逆转录酶（hTRT）最近被鉴定为一种假定的人端粒酶催化亚基。我们将编码hTRT的基因转染到端粒酶阴性的人正常成纤维细胞中，结果表明野生型hTRT的表达可诱导端粒酶活性，而在其他逆转录酶中保守区域发生突变的hTRT突变体则不能。对20份肝细胞癌样本和19份非癌性肝组织样本检测了端粒酶活性以及hTRT、人端粒酶RNA组分（hTR；由TERC编码）和人端粒酶相关蛋白（hTLP1；由TEP1编码）的表达情况。观察到hTRT表达与端粒酶活性之间存在显著相关性。这些结果表明hTRT蛋白是人端粒酶的催化亚基，并且它在癌细胞中端粒酶的激活中起关键作用。
