Baykal Atac, Rosen Daniel, Zhou Chenyi, Liu Jinsong, Sahin Aysegul A
University of Texas M.D. Anderson Cancer Center, Department of Pathology, Houston, Texas, USA.
Adv Anat Pathol. 2004 Sep;11(5):262-8. doi: 10.1097/01.pap.0000138145.19258.64.
Human chromosomes have highly specialized structures at their ends termed telomeres, repetitive, non-coding DNA sequences (5'-TTAGGG-3'), ranging in size from 5 to 20 kb in human cells. These highly specialized structures prevent chromosome ends from being recognized as double-strand DNA breaks, and they also provide protection from destabilizing agents. The mechanism for maintaining telomere integrity is controlled by telomerase, a ribonucleoprotein enzyme that specifically restores telomere sequences lost during replication by using an intrinsic RNA component as a template for polymerization. Telomerase has two core functional components required for its activity: the catalytic subunit of human telomerase reverse transcriptase (hTERT) and a telomerase RNA template (hTR). Telomerase is activated in the majority of immortal cell lines in culture and in most malignant tumors. This review outlines our current understanding of telomerase in breast cancer development and critically evaluates potential utilities in diagnosis, prognosis, and therapy.
人类染色体末端具有高度特化的结构,称为端粒,它是重复的非编码DNA序列(5'-TTAGGG-3'),在人类细胞中大小从5到20千碱基对不等。这些高度特化的结构可防止染色体末端被识别为双链DNA断裂,还能保护染色体免受破坏稳定的因素影响。维持端粒完整性的机制由端粒酶控制,端粒酶是一种核糖核蛋白酶,它通过使用内在RNA成分作为聚合模板,特异性地恢复复制过程中丢失的端粒序列。端粒酶活性需要两个核心功能成分:人类端粒酶逆转录酶(hTERT)的催化亚基和端粒酶RNA模板(hTR)。端粒酶在大多数培养的永生化细胞系和大多数恶性肿瘤中被激活。本综述概述了我们目前对端粒酶在乳腺癌发展中的理解,并严格评估了其在诊断、预后和治疗中的潜在用途。