Szyf M
Department of Pharmacology and Therapeutics, McGill University, Montreal PQ H3G 1Y6, Canada.
Biochemistry (Mosc). 2005 May;70(5):533-49. doi: 10.1007/s10541-005-0147-7.
Cancer growth and metastasis require the coordinate change in gene expression of different sets of genes. While genetic alterations can account for some of these changes, it is becoming evident that many of the changes in gene expression observed are caused by epigenetic modifications. The epigenome consists of the chromatin and its modifications, the "histone code" as well as the pattern of distribution of covalent modifications of cytosines residing in the dinucleotide sequence CG by methylation. Although hypermethylation of tumor suppressor genes has attracted a significant amount of attention and inhibitors of DNA methylation were shown to activate methylated tumor suppressor genes and inhibit tumor growth, demethylation of critical genes plays a critical role in cancer as well. This review discusses the emerging role of demethylation in activation of pro-metastatic genes and the potential therapeutic implications of the demethylation machinery in metastasis.
癌症的生长和转移需要不同基因集的基因表达发生协同变化。虽然基因改变可以解释其中一些变化，但越来越明显的是，观察到的许多基因表达变化是由表观遗传修饰引起的。表观基因组由染色质及其修饰、“组蛋白密码”以及通过甲基化作用于二核苷酸序列CG中胞嘧啶的共价修饰分布模式组成。尽管肿瘤抑制基因的高甲基化已引起了大量关注，并且DNA甲基化抑制剂已被证明可激活甲基化的肿瘤抑制基因并抑制肿瘤生长，但关键基因的去甲基化在癌症中也起着关键作用。本文综述讨论了去甲基化在促转移基因激活中的新作用以及去甲基化机制在转移中的潜在治疗意义。
