Dhaene K, Hübner R, Kumar-Singh S, Weyn B, Van Marck E
Department of Pathology, University of Antwerp, Wilrijk, Belgium.
Thorax. 1998 Nov;53(11):915-8. doi: 10.1136/thx.53.11.915.
Gradual telomere erosion eventually limits the replicative life span of somatic cells and is regarded as an ultimate tumour suppressor mechanism, eliminating cells that have accumulated genetic alterations. Telomerase, which has been found in over 85% of human cancers, elongates telomeres and may be required for tumorigenesis by the process of immortalisation. Malignant mesothelioma is an incurable malignancy with a poor prognosis. The disease becomes symptomatic decades after exposure to carcinogenic asbestos fibres, suggesting the long term survival of pre-malignant cell clones. This study investigated the presence of telomerase in pleural malignant mesothelioma, which may be the target for future anti-telomerase drugs.
Telomerase activity was semiquantitatively measured in extracts from 22 primary pleural mesotheliomas, two benign solitary fibrous tumours of the pleura, four mesothelioma cell lines, and six short term mesothelial cell cultures from normal pleura using a non-isotopic dilution assay of the telomeric repeat amplification protocol.
Twenty of the 22 primary mesotheliomas (91%) and all tumour derived mesothelioma cell lines were telomerase positive. Different levels of enzyme activity were observed in the tumours of different histological subtypes. Telomerase activity could not be detected in the six normal mesothelial cell cultures or in the two mesotheliomas. Both benign solitary fibrous tumours showed strong telomerase activity.
Telomerase activity is found in a high proportion of mesotheliomas and anti-telomerase drugs might therefore be useful clinically. The results are consistent with the hypothesis that telomerase activity may be a feature of carcinogenesis in mesotheliomas and possibly in many other cancers.
端粒的逐渐缩短最终会限制体细胞的复制寿命，被视为一种终极的肿瘤抑制机制，可清除积累了基因改变的细胞。端粒酶在超过85%的人类癌症中被发现，它能延长端粒，可能是肿瘤发生过程中永生所必需的。恶性间皮瘤是一种无法治愈的恶性肿瘤，预后很差。该疾病在接触致癌性石棉纤维数十年后才出现症状，这表明癌前细胞克隆能够长期存活。本研究调查了胸膜恶性间皮瘤中端粒酶的存在情况，端粒酶可能是未来抗端粒酶药物的靶点。
采用端粒重复序列扩增法的非同位素稀释检测法，对22例原发性胸膜间皮瘤、2例胸膜良性孤立性纤维瘤、4株间皮瘤细胞系以及6例来自正常胸膜的短期间皮细胞培养物的提取物中的端粒酶活性进行半定量测定。
22例原发性间皮瘤中有20例（91%）以及所有肿瘤来源的间皮瘤细胞系端粒酶呈阳性。在不同组织学亚型的肿瘤中观察到了不同水平的酶活性。在6例正常间皮细胞培养物或2例间皮瘤中未检测到端粒酶活性。2例良性孤立性纤维瘤均显示出较强的端粒酶活性。
在高比例的间皮瘤中发现了端粒酶活性，因此抗端粒酶药物可能在临床上有用。这些结果与端粒酶活性可能是间皮瘤以及可能许多其他癌症致癌过程中的一个特征这一假设一致。
