脑肿瘤组织中O^6-甲基鸟嘌呤-DNA甲基转移酶表达的研究  

STUDY ON EXPRESSION OF O 6 METHYLGUANINE DNA METHYLTRANSFERASE (MGMT) IN HUMAN BRAIN TUMORS

作　　者：官卫[1,2,3] 黄强[1,2,3] 龚德生[1,2,3] 陈忠平[1,2,3] 王爱东[1,2,3] 周丽英[1,2,3] 

机构地区：[1]苏州医学院附二院 [2]苏州医学院神经科学研究所脑肿瘤研究室 [3]苏州医学院附三院神经外科

出　　处：《肿瘤》1999年第4期206-208,共3页Tumor

摘　　要：探讨Ｏ６┐甲基鸟嘌呤┐ＤＮＡ甲基转移酶（ＭＧＭＴ）表达与脑肿瘤对氯乙基亚硝脲（ＣＥＮＵｓ）耐药的关系。方法采用Ｗｅｓｔｅｒｎｂｌｏｔ方法检测５９例不同类型脑肿瘤组织ＭＧＭＴ蛋白表达水平，对其中３０例胶质瘤同时采用ＲＴ┐ＰＣＲ检测其ＭＧＭＴｍＲＮＡ表达水平，ＭＧＭＴｍＲＮＡ表达水平与ＭＧＭＴ活性进行相关分析。结果ＭＧＭＴｍＲＮＡ表达水平与ＭＧＭＴ活性正相关（ｒ＝０．９１１，Ｐ＜０．０１），非胶质瘤及转移癌ＭＧＭＴ蛋白表达阳性率明显较胶质瘤高，分别为９０％，７８％，７％（Ｐ＜０．０５）；不同个体胶质瘤ＭＧＭＴｍＲＮＡ表达有较大异质性，范围为０～１．２９，平均为０．５±０．３７，Ｍｅｒ－率为３７％；高、低级别星形细胞瘤ＭＧＭＴｍＲＮＡ表达无差异（０．４７±０．３６和０．４４±０．３４）；髓母细胞瘤有较高的ＭＧＭＴｍＲＮＡ表达水平（０．８０）。结论胶质瘤ＭＧＭＴ总体水平较低，为此ＣＥＮＵｓ作为化疗首选药提供了新的理论依据；但半数以上胶质瘤为Ｍｅｒ＋表型，提示对ＣＥＮＵｓ耐药，因而化疗前检测Ｍｅｒ表型以筛选Ｍｅｒ－个体进行化疗将进一步提高疗效。Objective:To explore the relationship of the expression of MGMT with resistance of brain tumors to CENU.Methods:The levels of MGMT protein expression in 59 brain tumors were determined by Western blot analysis, of which the MGMT mRNA of 30 gliomas was measured by the use of RT PCR.Results:MGMT mRNA expression was well correlated with MGMT activity (r=0 911, P <0 01).The positive incidences of MGMT protein expression in non gliomas and brain metastatic carcinomas were significantly higher than gliomas (98%, 78%, 7% respectively, P <0 05). The MGMT mRNA value of gliomas was 0 50±0 37 fmol/mg (mean±s). The incidence of Mer - status in gliomas was 37%. No difference was observed between high grade astrocytomas and low grade ones(0 47±0 36 vs 0 44±0 34). Medulloblastomas had a little higher MGMT mRNA level (0 8). Conclusion:Generally low level of MGMT expression in gliomas was a molecular basis for effective chloroethylnitrosourea (CENU) chemotherapy. A large fraction of gliomas were Mer + indicating resistance to CENU. Screening Mer tumors for selective chemotherapy with CENU may enhance clinical therapeutic effect.

关 键 词：脑肿瘤 MGMT 治疗 耐药性 

分 类 号：R739.410.5[医药卫生—肿瘤]