Kyo S, Kanaya T, Takakura M, Tanaka M, Yamashita A, Inoue H, Inoue M
Department of Obstetrics and Gynecology, School of Medicine, Kanazawa University, Ishikawa, Japan.
Int J Cancer. 1999 Mar 15;80(6):804-9. doi: 10.1002/(sici)1097-0215(19990315)80:6<804::aid-ijc2>3.0.co;2-b.
Telomerase activity is involved in the maintenance of telomere length and is thought to be required for cellular immortality and oncogenesis. Three major subunits composing telomerase, human telomerase RNA (hTR), telomerase-associated protein (TPI) and human telomerase catalytic subunit (hTERT), have been identified. However, their functions and the regulatory mechanisms by which telomerase is activated have not been fully determined. In the present study, a total of 35 epithelial ovarian cancers, 5 ovarian low potential malignancies (LPM), 11 ovarian benign cysts and 12 normal ovaries, as well as various cell lines derived from ovarian cancers, were examined for the expression of hTR, TPI mRNA and hTERT mRNA. Correlations of expression with telomerase activity were evaluated. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that hTR and TPI mRNA were expressed in more than 80% of ovarian cancers, LPM, ovarian cysts and even in normal ovaries. However, hTERT mRNA was observed only in ovarian cancers, most of which exhibited telomerase activity. Normal ovarian tissues, ovarian cysts and LPM, most of which had no telomerase activity, did not express hTERT. Five telomerase-positive ovarian cancer cell lines expressed each of the telomerase subunits, whereas 2 telomerase-negative normal primary fibroblast cell lines expressed TPI mRNA and hTR, but not hTERT mRNA. There was a significant correlation of telomerase activity with hTERT mRNA expression but not with TPI or hTR expression. Expression of hTERT is thus specific to cancer lesions and appears to be a rate-limiting determinant of the enzymatic activity of human telomerase. Up-regulation of hTERT may play a critically important role in the development of ovarian cancers.
端粒酶活性参与端粒长度的维持，被认为是细胞永生化和肿瘤发生所必需的。构成端粒酶的三个主要亚基，即人端粒酶RNA（hTR）、端粒酶相关蛋白（TPI）和人端粒酶催化亚基（hTERT），已被鉴定出来。然而，它们的功能以及端粒酶被激活的调控机制尚未完全明确。在本研究中，共检测了35例上皮性卵巢癌、5例卵巢低潜在恶性肿瘤（LPM）、11例卵巢良性囊肿、12例正常卵巢以及源自卵巢癌的各种细胞系中hTR、TPI mRNA和hTERT mRNA的表达情况。评估了这些表达与端粒酶活性的相关性。逆转录-聚合酶链反应（RT-PCR）分析显示，hTR和TPI mRNA在超过80%的卵巢癌、LPM、卵巢囊肿甚至正常卵巢中均有表达。然而，hTERT mRNA仅在卵巢癌中观察到，其中大多数表现出端粒酶活性。正常卵巢组织、卵巢囊肿和LPM，其中大多数没有端粒酶活性，不表达hTERT。五个端粒酶阳性的卵巢癌细胞系表达了每个端粒酶亚基，而两个端粒酶阴性的正常原代成纤维细胞系表达TPI mRNA和hTR，但不表达hTERT mRNA。端粒酶活性与hTERT mRNA表达之间存在显著相关性，但与TPI或hTR表达无关。因此，hTERT的表达对癌症病变具有特异性，似乎是人类端粒酶酶活性的限速决定因素。hTERT的上调可能在卵巢癌的发生发展中起至关重要的作用。
