Analysis of telomeric single-strand overhang length in human endometrial cancers
Analysis of telomeric single-strand overhang length in human endometrial cancers
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DOI：
10.1016/j.febslet.2005.04.021
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发表时间：
2005-05-23
期刊：
影响因子：
3.5
通讯作者：
Inoue, M
中科院分区：
文献类型：
--
作者：
Hashimoto, M;Kyo, S;Inoue, M
端粒3'端单链突出端（3'-OH）是端粒结构的关键组成部分。尽管端粒长度在多种人类癌症中已经得到了很好的分析，但没有关于癌症中3 '-OH长度的信息。在本研究中，我们用端粒-寡核苷酸连接法检测了正常和恶性子宫内膜的3 '-OH长度。尽管3 '-OH长度在患者之间变化，但在子宫内膜癌中观察到的3'-OH长度显著短于在来自正常子宫内膜的样品中发现的3 '-OH长度（P < 0.001：Student's t检验），这表明3'-OH长度的侵蚀诱导受损的端粒完整性和基因组不稳定性，导致致癌作用。有趣的是，我们发现，最具侵袭性的子宫内膜癌亚型的3 '-OH长度显著长于非侵袭性亚型的3'-OH长度（P < 0.001：Sheffe检验），这表明具有长3 '-OH长度的癌细胞由于其稳定的端粒末端而具有生长优势。相反，我们没有观察到端粒长度与子宫内膜癌临床病理特征之间的关系。这些结果表明，3 '-OH长度的侵蚀，而不是整个端粒长度，在子宫内膜癌发生中发挥作用。此外，长3 '-OH可作为肿瘤侵袭性表型的分子标志物。(c)2005年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
The 3' single-strand telomeric overhang (3'-OH) is a key component of telomere structure. Although telomere length has been well analyzed in a variety of human cancers, no information is available on the 3'-OH length in cancers. In the present study, we examined the 3'-OH length in normal and malignant endometria using telomere-oligonucleotide ligation assay. Although 3'-OH lengths varied among patients, 3'-OH length observed in endometrial cancers was significantly shorter than that found in samples derived from normal endometria (P < 0.001: Student's t-test), suggesting that erosion of 3'-OH length induces impaired telomeric integrity and genomic instability, leading to carcinogenesis. Interestingly, we found that the most aggressive subtypes of endometrial cancers harbored significantly longer 3'-OH length than those with non-aggressive subtypes (P < 0.001: Sheffe's test), suggesting that cancer cells with long 3'-OH length have growth advantage due to their stabilized telomere ends. In contrast, we failed to observe an association between overall telomere length and any clinicopathological characteristics of endometrial cancers. These findings suggest that erosion of 3'-OH length, rather than overall telomere length, play roles in endometrial carcinogenesis. Furthermore, long 3'-OH may serve as a molecular marker for aggressive phenotype of tumors. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.