Maes L, Kalala J P O, Cornelissen R, de Ridder L
Department of Histology, Ghent University, Louis Pasteurlaan 2, B-9000 Gent, Belgium.
Anticancer Res. 2006 May-Jun;26(3B):2295-300.
Telomere length maintenance is essential for tumorigenesis. Most human tumours stabilise their chromosome ends by telomerase, a specialised reverse transcriptase that adds telomeric repeats (TTAGGG) to these ends. The main components of this telomerase complex are a reverse transcriptase (hTERT) and an integral RNA component (hTR). Most typical meningiomas, however, do not have active telomerase, although some express the hTERT component. The aim of this study was to evaluate telomerase activity and its reverse transcriptase for 33 (30 typical and three atypical) meningiomas in vivo and in vitro.
Telomerase activity was examined by the telomeric repeat amplification protocol (TRAP) assay. The protein, telomerase reverse transcriptase, was visualised by immunohistochemistry.
In vivo, telomerase activity was detectable in one out of 30 typical meningiomas and in two out of three atypical meningiomas. hTERT protein expression in vivo was positive in 14 out of 33 (42%) cases. The mean percentage of positive nuclei was 12.9% (SD=21.0). In vitro, 22 out of 33 (66%) meningiomas were positive for hTERT, with a mean percentage of positive nuclei of 31.8% (SD=37.1). Only four expressed telomerase activity in vitro, from which three had expressed telomerase activity in vivo. A significant association was found for telomerase activity (p<0.001) and hTERT expression (p<0.001) in vivo versus in vitro; a significant association was found for hTERT expression and telomerase activity in vivo (p<0.05) and in vitro (p<0.05).
The results of our study suggest that hTERT expression is an early event in carcinogenesis in contrast to telomerase activity. Fast-proliferating hTERT-positive tumour cells may overgrow in vitro by clonal selection.
端粒长度维持对肿瘤发生至关重要。大多数人类肿瘤通过端粒酶稳定其染色体末端，端粒酶是一种特殊的逆转录酶，可在这些末端添加端粒重复序列（TTAGGG）。该端粒酶复合物的主要成分是逆转录酶（hTERT）和一个完整的RNA成分（hTR）。然而，大多数典型的脑膜瘤没有活性端粒酶，尽管有些表达hTERT成分。本研究的目的是评估33例（30例典型和3例非典型）脑膜瘤在体内和体外的端粒酶活性及其逆转录酶。
通过端粒重复序列扩增协议（TRAP）测定法检测端粒酶活性。通过免疫组织化学观察端粒酶逆转录酶蛋白。
在体内，30例典型脑膜瘤中有1例可检测到端粒酶活性，3例非典型脑膜瘤中有2例可检测到。33例（42%）病例中，体内hTERT蛋白表达呈阳性。阳性细胞核的平均百分比为12.9%（标准差=21.0）。在体外，33例脑膜瘤中有22例（66%）hTERT呈阳性，阳性细胞核的平均百分比为31.8%（标准差=37.1）。体外只有4例表达端粒酶活性，其中3例在体内表达端粒酶活性。体内与体外的端粒酶活性（p<0.001）和hTERT表达（p<0.001）之间存在显著相关性；体内（p<0.05）和体外（p<0.05）的hTERT表达与端粒酶活性之间存在显著相关性。
我们的研究结果表明，与端粒酶活性相比，hTERT表达是致癌过程中的早期事件。快速增殖的hTERT阳性肿瘤细胞可能通过克隆选择在体外过度生长。
