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人类结直肠癌中端粒缩短与衰老。

Telomere reduction in human colorectal carcinoma and with ageing.

作者信息

Hastie N D, Dempster M, Dunlop M G, Thompson A M, Green D K, Allshire R C

机构信息

MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.

出版信息

Nature. 1990 Aug 30;346(6287):866-8. doi: 10.1038/346866a0.

Abstract

We have hypothesized that end-to-end chromosome fusions observed in some tumours could play a part in genetic instability associated with tumorigenesis and that fusion may result from the loss of the long stretches of G-rich repeats found at the ends of all linear chromosomes. We therefore asked whether there is telomere loss or reduction in common tumours. Here we show that in most of the colorectal carcinomas that we analysed, there is a reduction in the length of telomere repeat arrays relative to the normal colonic mucosa from the same patient. We speculate on the consequences of this loss for tumorigenesis. We also show that the telomere arrays are much smaller in colonic mucosa and blood than in fetal tissue and sperm, and that there is a reduction in average telomere length with age in blood and colon mucosa. We propose that the telomerase is inactive in somatic tissues, and that telomere length is an indicator of the number of cell divisions that it has taken to form a particular tissue and possibly to generate tumours.

摘要

我们曾推测,在某些肿瘤中观察到的端对端染色体融合可能在与肿瘤发生相关的基因不稳定中起作用,并且这种融合可能是由于所有线性染色体末端富含G的重复序列长片段缺失所致。因此,我们询问在常见肿瘤中是否存在端粒缺失或缩短。在此我们表明,在我们分析的大多数结肠直肠癌中,相对于同一患者的正常结肠黏膜,端粒重复序列阵列的长度有所缩短。我们推测了这种缺失对肿瘤发生的影响。我们还表明,结肠黏膜和血液中的端粒阵列比胎儿组织和精子中的小得多,并且血液和结肠黏膜中的平均端粒长度会随着年龄增长而缩短。我们提出,端粒酶在体细胞组织中无活性,并且端粒长度是形成特定组织以及可能产生肿瘤所需细胞分裂次数的一个指标。

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