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癌症中的表观遗传基因沉默——早期致癌途径成瘾的一种机制?

Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction?

作者信息

Baylin Stephen B, Ohm Joyce E

机构信息

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Bunting-Blaustein Cancer Research Building, 1650 Orleans Street, Suite 530, Baltimore, Maryland 21231, USA.

出版信息

Nat Rev Cancer. 2006 Feb;6(2):107-16. doi: 10.1038/nrc1799.

Abstract

Chromatin alterations have been associated with all stages of tumour formation and progression. The best characterized are epigenetically mediated transcriptional-silencing events that are associated with increases in DNA methylation - particularly at promoter regions of genes that regulate important cell functions. Recent evidence indicates that epigenetic changes might 'addict' cancer cells to altered signal-transduction pathways during the early stages of tumour development. Dependence on these pathways for cell proliferation or survival allows them to acquire genetic mutations in the same pathways, providing the cell with selective advantages that promote tumour progression. Strategies to reverse epigenetic gene silencing might therefore be useful in cancer prevention and therapy.

摘要

染色质改变与肿瘤形成和进展的各个阶段都有关联。其中研究最为深入的是表观遗传介导的转录沉默事件,这些事件与DNA甲基化增加有关,尤其是在调控重要细胞功能的基因启动子区域。最近的证据表明,表观遗传变化可能使癌细胞在肿瘤发展早期对改变的信号转导通路产生“依赖”。细胞增殖或存活对这些通路的依赖使得它们在相同通路中获得基因突变,从而为细胞提供促进肿瘤进展的选择性优势。因此,逆转表观遗传基因沉默的策略可能对癌症预防和治疗有用。

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