Yoshida K, Sugino T, Goodison S, Warren B F, Nolan D, Wadsworth S, Mortensen N J, Toge T, Tahara E, Tarin D
Nuffield Department of Pathology and Bacteriology, University of Oxford, UK.
Br J Cancer. 1997;75(4):548-53. doi: 10.1038/bjc.1997.96.
Telomerase is a ribonucleoprotein capable of replacing telomeric DNA sequences that are lost at each cell division. Under normal circumstances, it is active in rapidly dividing embryonic cells and in stem cell populations but not in terminally differentiated somatic cells. Much attention has recently focused on the hypothesis that activity of this enzyme is necessary for cells to become immortal. This predicts that telomerase activity should be detectable in malignant cells and tissues but not in their normal counterparts, which slowly senesce and die. In accordance with this notion, telomerase activity has been reported in a wide range of malignancies, including those of the gastrointestinal tract, breast and lung. In the present study, we used a polymerase chain reaction (PCR)-based assay for telomerase activity, designated the "telomeric repeat amplification protocol (TRAP)', to examine initially 35 colonic carcinomas, their corresponding normal tissues and 12 inflammatory bowel disease (IBD) lesions. We detected strong enzyme activity in 32 (92%) of the 35 colon carcinomas while there was no activity in 30 (86%) of 35 matched normal colonic tissue specimens and only very weak activity in the remainder. Four of seven specimens of ulcerative colitis and two of five Crohn's disease lesions were negative, and the rest were only weakly positive. These results led us to examine whether telomerase could be detected in carcinoma cells exfoliated into the colonic lumen. We assayed lysates of exfoliated cells in luminal washings from colectomy specimens of 15 patients with colon carcinoma and nine with IBD. Telomerase activity was detected in washings from 9 (60%) of the 15 colon carcinoma cases but not in any from cases with IBD, suggesting that it can be a good marker for the detection of colon carcinoma, possibly even in non-invasively obtained samples.
端粒酶是一种核糖核蛋白，能够替代在每次细胞分裂时丢失的端粒DNA序列。在正常情况下，它在快速分裂的胚胎细胞和干细胞群体中具有活性，但在终末分化的体细胞中则无活性。最近，很多注意力都集中在这样一种假说上，即这种酶的活性对于细胞成为永生细胞是必需的。这预示着在恶性细胞和组织中应该能够检测到端粒酶活性，而在正常对应组织中则检测不到，因为正常组织会缓慢衰老并死亡。根据这一观点，已经报道在多种恶性肿瘤中检测到了端粒酶活性，包括胃肠道、乳腺和肺部的恶性肿瘤。在本研究中，我们使用一种基于聚合酶链反应（PCR）的端粒酶活性检测方法，即“端粒重复序列扩增法（TRAP）”，首先检测了35例结肠癌、其相应的正常组织以及12例炎症性肠病（IBD）病变。我们在35例结肠癌中的32例（92%）检测到了很强的酶活性，而在35例匹配的正常结肠组织标本中的30例（86%）未检测到活性，其余标本仅检测到非常微弱的活性。7例溃疡性结肠炎标本中有4例以及5例克罗恩病病变中有2例为阴性，其余仅为弱阳性。这些结果促使我们去检测是否能够在脱落到结肠腔中的癌细胞中检测到端粒酶。我们检测了15例结肠癌患者和9例IBD患者结肠切除标本的腔内冲洗液中脱落细胞的裂解物。在15例结肠癌病例中的9例（60%）的冲洗液中检测到了端粒酶活性，而IBD病例的冲洗液中均未检测到，这表明端粒酶可能是检测结肠癌的一个良好标志物，甚至可能适用于非侵入性获取的样本。
