Kanaya T, Kyo S, Takakura M, Ito H, Namiki M, Inoue M
Department of Obstetrics and Gynecology, School of Medicine, Kanazawa University, Ishikawa, Japan.
Int J Cancer. 1998 Nov 23;78(5):539-43. doi: 10.1002/(sici)1097-0215(19981123)78:5<539::aid-ijc2>3.0.co;2-i.
Telomerase is a ribonucleoprotein enzyme which stabilizes chromosomal structure, thereby inducing cellular immortality. Three major subunits composing telomerase complex have been cloned, designated hTR (human telomerase RNA), TPI (telomerase-associated protein I), and hTERT (human telomerase reverse transcriptase). In the present study, a total of 36 renal-cell carcinomas (RCC) and adjacent normal tissues, as well as cell lines derived from RCC or normal kidney, were examined for the expression of each telomerase subunit and telomerase activity. RT-PCR analyses revealed that hTR and TP I mRNA were constitutively expressed both in tumor and in normal tissues. In contrast, hTERT mRNA was expressed in most tumors, but not in normal tissues. Telomeric-repeat-amplification-protocol (TRAP) assay revealed that more than 80% of RCC tumor tissue exhibited telomerase activity, while none of the adjacent normal tissue did. There was a significant association of telomerase activity with expression of hTERT mRNA, but not with TPI mRNA or hTR expression. Two cell lines, derived from RCC and cervical cancer, expressed telomerase activity and hTERT mRNA, while normal renal cortical epithelial cells expressed neither of them. These findings suggest that hTERT plays a critical role in determining the enzymatic activity of human telomerase, and that up-regulation of hTERT probably plays a role in the progression of human cancers.
端粒酶是一种核糖核蛋白酶，可稳定染色体结构，从而诱导细胞永生化。构成端粒酶复合物的三个主要亚基已被克隆，分别命名为hTR（人类端粒酶RNA）、TPI（端粒酶相关蛋白I）和hTERT（人类端粒酶逆转录酶）。在本研究中，共检测了36例肾细胞癌（RCC）及其癌旁正常组织，以及源自RCC或正常肾的细胞系中各端粒酶亚基的表达和端粒酶活性。逆转录-聚合酶链反应（RT-PCR）分析显示，hTR和TPI mRNA在肿瘤组织和正常组织中均持续表达。相比之下，hTERT mRNA在大多数肿瘤组织中表达，但在正常组织中不表达。端粒重复序列扩增法（TRAP）检测显示，超过80%的RCC肿瘤组织表现出端粒酶活性，而癌旁正常组织均未表现出该活性。端粒酶活性与hTERT mRNA的表达显著相关，但与TPI mRNA或hTR的表达无关。源自RCC和宫颈癌的两个细胞系表达端粒酶活性和hTERT mRNA，而正常肾皮质上皮细胞均不表达。这些发现表明，hTERT在决定人类端粒酶的酶活性方面起关键作用，并且hTERT的上调可能在人类癌症进展中起作用。
