作为抗癌治疗靶点的DNA甲基化机制

The DNA methylation machinery as a target for anticancer therapy.

作者信息

Szyf M

机构信息

Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.

出版信息

Pharmacol Ther. 1996;70(1):1-37. doi: 10.1016/0163-7258(96)00002-2.

DOI:10.1016/0163-7258(96)00002-2

PMID:8804109

Abstract

DNA methylation is now recognized as an important mechanism regulating different functions of the genome; gene expression, replication, and cancer. Different factors control the formation and maintenance of DNA methylation patterns. The level of activity of DNA methyltransferase (MeTase) is one factor. Recent data suggest that some oncogenic pathways can induce DNA MeTase expression, that DNA MeTase activity is elevated in cancer, and that inhibition of DNA MeTase can reverse the transformed state. What are the pharmacological consequences of our current understanding of DNA methylation patterns formation? This review will discuss the possibility that DNA MeTase inhibitors can serve as important pharmacological and therapeutic tools in cancer and other genetic diseases.

摘要

DNA甲基化如今被公认为是一种调节基因组不同功能的重要机制，这些功能包括基因表达、复制以及癌症相关过程。不同的因素控制着DNA甲基化模式的形成与维持。DNA甲基转移酶（MeTase）的活性水平就是其中一个因素。近期数据表明，一些致癌途径可诱导DNA MeTase表达，在癌症中DNA MeTase活性升高，并且抑制DNA MeTase可逆转细胞的转化状态。基于我们目前对DNA甲基化模式形成的理解会产生哪些药理学后果呢？本综述将探讨DNA MeTase抑制剂能否作为癌症及其他遗传性疾病重要的药理学和治疗工具的可能性。