TELOMERASE ACTIVITY IN SMALL-CELL AND NON-SMALL-CELL LUNG CANCERS
TELOMERASE ACTIVITY IN SMALL-CELL AND NON-SMALL-CELL LUNG CANCERS
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DOI：
10.1093/jnci/87.12.895
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发表时间：
1995-06-21
期刊：
影响因子：
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通讯作者：
SHAY, JW
中科院分区：
文献类型：
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作者：
HIYAMA, K;HIYAMA, E;SHAY, JW
背景：端粒酶是一种将六聚体TTAGGG核苷酸重复序列添加到脊椎动物染色体DNA末端的酶（即，端粒）以补偿每一轮DNA复制中发生的损失。体细胞不具有端粒酶活性，并且当至少一些染色体的端粒末端缩短到临界长度时停止分裂。有人认为，永生化细胞（包括一些，但可能不是所有的癌细胞）继续无限期地增殖，因为它们表达端粒酶。目的：为了探讨端粒酶的表达是否是人类自然发生的癌症的发展的先决条件，我们检测了端粒酶活性在人类肺癌和癌旁正常组织标本的水平。研究方法：采用聚合酶链反应（PCR）方法检测了136例原发性肺癌组织和68例手术切除的癌旁组织中端粒酶活性。我们还研究了通过活检（2例）或尸检（10例）获得的4例原发性和23例转移性病变的端粒酶活性。通过对标本制备的提取物进行系列稀释来估计相对端粒酶活性水平。端粒酶活性也测定存在于胸水的细胞提取物从三个肺腺癌患者。结果如下：136例肺癌组织中109例（80.1%）端粒酶阳性，68例癌旁正常组织中3例（4.4%）端粒酶阳性。所有11例手术切除的原发性小细胞肺癌标本（来自11例患者）均显示高水平的端粒酶活性，而125例手术切除的原发性非小细胞肺癌组织标本（来自125例患者）的端粒酶活性范围从检测不到到高水平。一般来说，在转移性病变和端粒长度改变的肿瘤中观察到高水平的端粒酶活性。一些原发性肿瘤和令人惊讶的转移性肿瘤似乎没有检测到端粒酶活性。然而，端粒酶活性，检测细胞中存在的所有测试胸腔积液获得（从三个肺腺癌患者）。结论：仅表现出低水平或不可检测的端粒酶活性的非小细胞肺癌的亚组可能主要包含致死性癌细胞。显示高水平端粒酶活性的癌症，如本研究中检查的所有小细胞肺癌，可能主要由永生细胞组成。含义：端粒酶活性可作为临床诊断肺癌细胞永生化的标志物，也可作为治疗干预的靶点。
Background: Telomerase is an enzyme that adds hexameric TTAGGG nucleotide repeats onto the ends of vertebrate chromosomal DNAs (i.e., telomeres) to compensate for losses that occur with each round of DNA replication. Somatic cells do not have telomerase activity and stop dividing when the telomeric ends of at least some chromosomes have been shortened to a critical length. It has been suggested that immortalized cells (including some, but probably not all, cancer cells) continue to proliferate indefinitely because they express telomerase. Purpose: To investigate whether expression of telomerase is a prerequisite for the development of naturally occurring human cancers, we assayed the levels of telomerase activity in specimens of human lung tumor and adjacent normal tissue. Methods: Using a polymerase chain reaction-based assay, we examined telomerase activity in 136 primary lung cancer tissues and 68 adjacent noncancerous tissues obtained by surgical resection. We also studied telomerase activity in four primary and 23 metastatic lesions obtained through biopsy (two patients) or autopsy (10 patients). Relative telomerase activity levels were estimated by serial dilutions of extracts prepared from the specimens. Telomerase activity was also assayed in extracts of cells present in pleural fluids from three patients with adenocarcinoma of the lung. Results: Among surgically resected samples, telomerase activity was detected in 109 (80.1%) of 136 primary lung cancer tissues and in three (4.4%) of 68 normal adjacent tissues. All 11 surgically resected specimens of primary small-cell lung cancer (from 11 patients) revealed high levels of telomerase activity, whereas the activity ranged from undetectable to high levels in the 125 surgically resected specimens of primary nonsmall-cell lung cancer tissue (from 125 patients). Generally, high levels of telomerase activity were observed in metastatic lesions and tumors with altered telomere length. A few primary and, surprisingly, some metastatic tumors did not appear to have detectable telomerase activity. Telomerase activity was, however, detected in cells present in all tested pleural fluids obtained (from three patients with adenocarcinoma of the lung). Conclusion: The subset of non-small-cell lung cancers that exhibits only low or undetectable levels of telomerase activity may contain primarily mortal cancer cells. Cancers that exhibit high levels of telomerase activity, such as all of the small-cell lung cancers examined in this study, are likely to consist mainly of immortal cells. Implications: Telomerase activity may be useful both as a diagnostic marker to detect the existence of immortal lung cancer cells in clinical materials and as a target for therapeutic intervention.