Telomere shortening in renal cell carcinoma.
Telomere shortening in renal cell carcinoma.
复制标题
肾细胞癌中的端粒缩短。
作者：
C. Mehle;B. Ljungberg;G. Roos
人类染色体的末端由特化结构端粒组成，端粒由TTAGGG重复序列组成，根据年龄和组织的增殖活性，TTAGGG重复序列构成总共5-15个端粒酶对。端粒的主要功能是为染色体提供稳定性并保护潜在的独特编码序列免受降解。在体外人成纤维细胞和胚胎肾细胞中，在每次细胞分裂后估计端粒序列损失在50至65个碱基对/细胞分裂之间。这种丢失是由于每个端粒末端的一条链的DNA复制是不完整的。在低等真核生物中，存在由端粒酶提供的补偿机制，端粒酶在人体细胞中是无活性的。在体外永生化的人细胞中也检测到端粒酶活化。在这项研究中，我们分析了肾细胞癌端粒缩短的发生使用探针（TTAGGG）4。Southern印迹杂交显示，在所有10个分析的肿瘤中，2或3个肿瘤内样本的平均端粒限制性片段（TRF）长度缩短了0.4至2.5个端粒酶对。平均TRF长度值没有发现明显的瘤内异质性。然而，异质性表现为在10个肿瘤中的7个中出现至少两个单独的TRF峰值，表明存在不同的肿瘤细胞克隆。当我们评估杂交信号的强度时，我们发现了一个矛盾的观察结果，其中三个肿瘤显示杂交信号增加，尽管伴随着TRF减少。我们发现肿瘤大小和计算的肿瘤细胞分裂之间没有相关性。在两个肿瘤中，计算的细胞分裂周期与肿瘤大小相比不切实际地低。提示肾癌组织中可能存在端粒酶活性。
The ends of human chromosomes consist of a specialized structure, the telomere, composed of repeats of TTAGGG making up a total of 5-15 kilobase pairs, depending on age and proliferative activity of the tissue. The major function of telomeres is to provide stability to chromosomes and protect underlying unique coding sequences from degradation. There is a loss of telomeric sequences following every cell division estimated to be between 50 and 65 basepairs/cell division in human fibroblasts and embryonic kidney cells in vitro. This loss is due to the fact that DNA replication is incomplete for one strand at each telomere end. In lower eukaryotes there is a compensation mechanism provided by the enzyme telomerase, which is inactive in human somatic cells. Telomerase activation has also been detected in vitro immortalized human cells. In this study we analyzed renal cell carcinoma for the occurrence of telomere shortening using the probe (TTAGGG)4. Southern blots of HinfI-digested DNA revealed a shortening of mean telomere restriction fragment (TRF) length of 0.4 to 2.5 kilobase pairs in 2 or 3 intratumoral samples in all 10 tumors analyzed. No obvious intratumoral heterogeneity was found in mean TRF length values. However, heterogeneity was shown by the occurrence of at least two separate peak TRF values in 7 of 10 tumors, indicating the presence of different tumor cell clones. A conflicting observation was made when we evaluated the intensity of the hybridization signals, where three of the tumors showed an increase in hybridization signals despite concomitant TRF reduction. We found no correlation between tumor size and calculated tumor cell divisions undergone. In two tumors, the calculated cell division cycles were unrealistically low compared to the tumor size. These data suggest that telomerase activation might occur in human renal cell carcinoma.
影响因子：
11.1
作者：
V. Zakian
通讯作者：
V. Zakian
DOI：
10.1073/pnas.89.21.10114
发表时间：
1992-11-01
影响因子：
11.1
作者：
ALLSOPP, RC;VAZIRI, H;HARLEY, CB
通讯作者：
HARLEY, CB