Chong Ja-Mun, Sakuma Kazuya, Sudo Makoto, Ushiku Tetsuo, Uozaki Hiroshi, Shibahara Junji, Nagai Hideo, Funata Nobuaki, Taniguchi Hirokazu, Aburatani Hiroyuki, Fukayama Masashi
Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033.
Cancer Sci. 2003 Jan;94(1):76-80. doi: 10.1111/j.1349-7006.2003.tb01355.x.
DNA hypermethylation may play a primary role in the genesis of Epstein-Barr virus (EBV)-associated gastric carcinoma (GC) (EBVaGC). Methylation-specific PCR targeting CpG-islands demonstrated markedly increased methylation of specific genes, such as p14, p15 and p16 genes, in EBVaGC in vivo. A high frequency of methylation was observed in an EBVaGC strain of severe combined immunodeficiency mice, and the expression of methylated genes in the strain was apparently lower than the expression of the unmethylated genes in EBV-negative GC strains. Although over-expression of DNA methyltransferases (DNMTs) is known to be associated with some human cancers, real-time PCR demonstrated that DNMTs expression was suppressed in EBVaGC. The DNA methylation of specific genes, independently of DNMTs expression, may be important in the development of EBVaGC.
DNA高甲基化可能在爱泼斯坦-巴尔病毒(EBV)相关胃癌(EBVaGC)的发生中起主要作用。针对CpG岛的甲基化特异性PCR显示,在体内EBVaGC中,特定基因如p14、p15和p16基因的甲基化明显增加。在严重联合免疫缺陷小鼠的EBVaGC菌株中观察到高频率的甲基化,并且该菌株中甲基化基因的表达明显低于EBV阴性胃癌菌株中未甲基化基因的表达。虽然已知DNA甲基转移酶(DNMTs)的过表达与某些人类癌症有关,但实时PCR显示DNMTs在EBVaGC中表达受到抑制。特定基因的DNA甲基化,独立于DNMTs的表达,可能在EBVaGC的发展中起重要作用。