Nishi H, Ohyashiki K, Fujito A, Yahata N, Ohyashiki J H, Isaka K, Takayama M
Department of Obstetrics and Gynecology, Tokyo Medical University, Japan.
Placenta. 1999 May;20(4):317-23. doi: 10.1053/plac.1998.0386.
Activation of telomerase compensating for the loss of telomeres has been implicated in human cell immortalization and carcinogenesis. Telomeric repeat amplification protocol (TRAP) assay can be used to detect telomerase activity in a variety of malignant tumours, including those of the female reproductive tract which have been found to have high levels of telomerase activity. However, it is unclear whether all the cells or only a subset of cells within a tumour have telomerase activity. To determine the regulation mechanism of telomerase activity in hydatidiform moles, we studied telomerase activity at the single cell level (using an in situ TRAP assay), and expression of TLP1 (telomerase protein 1), TERC (telomerase RNA component) and TERT (telomerase reverse transcriptase component). Expression of TERC and TLP1 was observed in all normal chorionic villi, as well as in trophoblastic diseases, and various cell lines irrespective of telomerase activity. TERT expression was observed in trophoblastic diseases and normal chorionic villi with telomerase activity but not in normal chorionic villi without telomerase activity, except in some cases in the present series, indicating that TERT expression is closely associated with telomerase activity. Upregulation of TERT expression may thus play an important role in telomerase reactivation.
端粒酶激活以补偿端粒的缺失与人类细胞永生化和致癌作用有关。端粒重复序列扩增法（TRAP）检测可用于检测多种恶性肿瘤中的端粒酶活性，包括已发现具有高水平端粒酶活性的女性生殖道肿瘤。然而，尚不清楚肿瘤内所有细胞还是仅一部分细胞具有端粒酶活性。为了确定葡萄胎中端粒酶活性的调控机制，我们在单细胞水平研究了端粒酶活性（使用原位TRAP检测）以及端粒酶蛋白1（TLP1）、端粒酶RNA组分（TERC）和端粒酶逆转录酶组分（TERT）的表达。在所有正常绒毛膜绒毛、滋养层疾病以及各种细胞系中均观察到TERC和TLP1的表达，而与端粒酶活性无关。在具有端粒酶活性的滋养层疾病和正常绒毛膜绒毛中观察到TERT表达，但在无端粒酶活性的正常绒毛膜绒毛中未观察到TERT表达，本研究系列中的某些病例除外，这表明TERT表达与端粒酶活性密切相关。因此，TERT表达上调可能在端粒酶重新激活中起重要作用。
