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O6-烷基鸟嘌呤-DNA-烷基转移酶(AGAT),由肿瘤抑制基因agat编码,能够修复甲基亚硝脲(MNU)等烷化剂造成的损伤,减少肿瘤的发生。然而,当agat基因因其启动子CpG岛发生异常甲基化导致其基因沉默(gene scilencing)时,agat不能正常表达,细胞中AGAT活性降低,DNA受到烷化剂的作用,发生G:C-A:C突变,进而引起肿瘤的发生、进展。另一方面,肿瘤细胞中AGAT活性较高时,将对同为重要化疗药物的烷化剂产生耐药性。综述近年来胃癌组织中agat基因异常甲基化及其在胃癌发生和治疗中的研究进展。
O6-alkylguanine-DNA-alkyltransferase (AGAT), encoded by the tumor suppressor gene agat, can repair the damage caused by alkylating agents such as methylnitrosourea (MNU) and reduce the occurrence of tumors. However, when the agat gene is genely sclencing due to the abnormal methylation of its promoter CpG island, agat can not be normally expressed, AGAT activity decreases in cells, DNA is alkylated, and G: CA: C mutation, and then cause the occurrence of tumor, progress. On the other hand, higher AGAT activity in tumor cells will develop resistance to alkylating agents that are important chemotherapeutic drugs. This review summarizes the abnormal methylation of agat gene in gastric cancer tissue and its progress in the development and treatment of gastric cancer in recent years.