Mehle C, Piatyszek M A, Ljungberg B, Shay J W, Roos G
Department of Pathology, Umea University, Sweden.
Oncogene. 1996 Jul 4;13(1):161-6.
Telomeres have a vital role in maintaining chromosome stability and are essential for long term viability. Since the very ends of linear chromosomes cannot replicate, telomeres shorten in normal somatic cells eventually resulting in growth inhibition. However, most immortal cell lines maintain stable telomeres indicating that mechanisms exist to compensate for the end replication problem. Telomerase activity, leading to synthesis of telomeric DNA repeats, has been proposed to be an important step in the immortalization process of tumor cells. In the present study, 56 renal cell carcinomas were tested for telomerase activity using the sensitive TRAP (telomeric repeat amplification protocol). Forty of the analysed tumors (71%) were positive for telomerase activity, whereas none of the 56 corresponding normal kidney samples showed telomerase activity. All telomerase negative tumors had a reduction in mean telomere restriction fragment (TRF) length and a decrease in total telomere repeat hybridization signal, though cases were observed with an increase in peak TRF lengths. No obvious association between the presence of telomerase activity and clinicopathological parameters (histopathologic grade, DNA-ploidy, stage and clinical outcome) was found. The high frequency of detection of telomerase activity in the renal cell carcinomas indicates that this enzyme is likely to be an important factor involved in the evolution of this tumor type.
端粒在维持染色体稳定性方面起着至关重要的作用，对长期生存能力至关重要。由于线性染色体的末端无法复制，端粒在正常体细胞中会缩短，最终导致生长抑制。然而，大多数永生细胞系维持稳定的端粒，这表明存在补偿末端复制问题的机制。端粒酶活性可导致端粒DNA重复序列的合成，被认为是肿瘤细胞永生化过程中的一个重要步骤。在本研究中，使用灵敏的端粒重复序列扩增法（TRAP）检测了56例肾细胞癌的端粒酶活性。在所分析的肿瘤中，40例（71%）端粒酶活性呈阳性，而56例相应的正常肾组织样本均未显示端粒酶活性。所有端粒酶阴性的肿瘤平均端粒限制片段（TRF）长度均缩短，端粒重复序列杂交信号总量减少，不过也观察到有峰值TRF长度增加的病例。未发现端粒酶活性的存在与临床病理参数（组织病理学分级、DNA倍体、分期和临床结果）之间存在明显关联。肾细胞癌中端粒酶活性的高检出频率表明，该酶可能是参与这种肿瘤类型演变的一个重要因素。
