Gopisetty Gopal, Ramachandran Kavitha, Singal Rakesh
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Mol Immunol. 2006 Apr;43(11):1729-40. doi: 10.1016/j.molimm.2005.11.010. Epub 2006 Feb 28.
DNA methylation is an epigenetic phenomenon known to play an increasingly important role in the etiology of cancer. Changes in DNA methylation patterns particularly in the promoter region of genes either in the form of hypomethylation or hypermethylation can have profound effects on gene expression. Hypermethylation in the promoter region of genes is involved in down regulation of the gene expression. Studies from various cancers have revealed that DNA methylation affects genes involved in different cellular pathways including apoptosis. Apoptosis or programmed cell death plays a vital role in the maintenance of cellular homeostasis, i.e. a balance between cell proliferation and cell death. Cancer cells are known to harbor defects in apoptotic pathway and disruption of apoptosis is considered as an important factor aiding its evolution. Evidence from literature indicates that DNA methylation mediated down regulation of genes involved in apoptosis could be a significant mechanism through which tumor cells avoid apoptosis.
DNA甲基化是一种表观遗传现象,已知其在癌症病因学中发挥着越来越重要的作用。DNA甲基化模式的改变,特别是基因启动子区域以低甲基化或高甲基化形式出现的改变,可对基因表达产生深远影响。基因启动子区域的高甲基化参与基因表达的下调。来自各种癌症的研究表明,DNA甲基化会影响参与包括凋亡在内的不同细胞途径的基因。凋亡或程序性细胞死亡在维持细胞稳态中起着至关重要的作用,即细胞增殖与细胞死亡之间的平衡。已知癌细胞在凋亡途径中存在缺陷,而凋亡的破坏被认为是促进其演变的一个重要因素。文献证据表明,DNA甲基化介导的参与凋亡的基因下调可能是肿瘤细胞逃避凋亡的一个重要机制。