Szyf Moshe, Pakneshan Pouya, Rabbani Shafaat A
Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Que., Canada PQ H3G 1Y6.
Cancer Lett. 2004 Aug 10;211(2):133-43. doi: 10.1016/j.canlet.2004.04.009.
The epigenome, which is comprised of chromatin and its associated proteins and the patterns of covalent modification of DNA by methylation, sets up and maintains gene expression programs. A hallmark of cancer is a paradoxical aberration of DNA methylation patterns, a global loss of DNA methylation, that coexists with regional hypermethylation of certain genes. The hypermethylation of tumor-suppressor genes has attracted significant attention recently and DNA methylation inhibitors are being tested as potential anticancer agents. However, emerging data suggests that hypomethylation plays a role in activating genes required for metastasis and invasion. It is proposed here that hypermethylation and hypomethylation in cancer are independent processes, which target different programs at different stages in tumorigenesis. Understanding the relative roles of hypomethylation and hypermethylation in cancer has clear implications on the therapeutic use of agents targeting the DNA methylation machinery, which are discussed in this review.
表观基因组由染色质及其相关蛋白质以及通过甲基化对DNA进行共价修饰的模式组成，它建立并维持基因表达程序。癌症的一个标志是DNA甲基化模式的自相矛盾的异常，即DNA甲基化的整体缺失，它与某些基因的区域高甲基化共存。肿瘤抑制基因的高甲基化最近引起了极大关注，DNA甲基化抑制剂正在作为潜在的抗癌药物进行测试。然而，新出现的数据表明，低甲基化在激活转移和侵袭所需的基因中起作用。本文提出，癌症中的高甲基化和低甲基化是独立的过程，它们在肿瘤发生的不同阶段针对不同的程序。了解低甲基化和高甲基化在癌症中的相对作用对靶向DNA甲基化机制的药物的治疗应用具有明确的意义，本文将对此进行讨论。
