DNA甲基转移酶1基因在人肝外胆管癌组织和细胞中的表达及意义  

The Expression and Significance of DNA Methyltransferase 1 Gene in Extrahepatic Cholangiocarcinoma Tissues and Cells

作　　者：左石[1] 邹声泉[2] 孙诚谊[1] 

机构地区：[1]贵阳医学院附院肝胆外科,贵州贵阳550004 [2]华中科技大学同济医学院附属同济医院普外Ⅱ科,湖北武汉430030

出　　处：《贵阳医学院学报》2011年第3期221-225,共5页Journal of Guiyang Medical College

基　　金：国家"863计划"资助项目(No.2002AA214061);贵州省科技厅2010年度社发攻关计划项目[黔科合(2010)3162]

摘　　要：目的:研究DNA甲基转移酶1(DNMT1)在人肝外胆管癌组织和人胆管癌细胞系QBC939中的表达,并分析DNMT1的表达与胆管癌临床病理因素之间的关系,探讨其在胆管癌发生发展过程中的作用。方法:用免疫组织化学法检测DNMT1在24例人肝外胆管癌组织和20例慢性胆管炎组织中的阳性细胞表达率,将二者进行对比并分析其与胆管癌临床病理之间的关系;用RT-PCR和Western Blot分别检测DNMT1在人胆管癌细胞系QBC939中转录水平和蛋白水平的表达情况。结果:(1)在24例胆管癌组织中DNMT1蛋白阳性细胞表达率为(37.57±11.24)%,而在20例伴慢性炎症的胆管壁组织中DNMT1蛋白阳性细胞表达率为(10.73±6.61)%,二者之间的差异具有显著性意义(P=0.005);(2)DNMT1蛋白的异常表达与胆管癌组织的分化程度相关,低分化肿瘤的表达水平最高,其次为中等分化肿瘤,高分化肿瘤的表达水平较低,DNMT1蛋白的异常表达与性别、年龄、肿瘤大小、肿瘤部位、有无淋巴结转移和临床分期无明显关系;(3)在人胆管癌细胞系QBC939中,通过RT-PCR和Western Blot均能检测到DNMT1基因mRNA和蛋白的表达。结论:(1)在胆管癌组织中,DNMT1蛋白的表达较慢性胆管炎组织明显增加,并与肿瘤组织分化程度有关,与性别、年龄、肿瘤大小、肿瘤部位、有无淋巴结转移和临床分期无明显关系,提示DNMT1的高表达可能与胆管癌的发生发展有关,且可能是胆管癌发生中的一个早期分子事件;(2)DNMT1在人胆管癌细胞系QBC939中存在表达。Objective：To study the expression of DNA methyltransferase 1（DNMT1） in human extrahepatic cholangiocarcinoma（ECC） tissues and cell line QBC939,and to analyze the relationship between the expression level of DNMT1 and clinicopathologic features of ECC,and so as to explore the roles of DNMT1 in the tumorigenesis of ECC.Methods：The expression of DNMT1 protein was detected in 24 ECC specimens and in 20 chronic cholangeitis tissue specimens with immunohistochemistry method.The results of the two kinds of tissues were compared,and their relationship with the clinicopatholigic features of ECC was analyzed.RT-PCR and Western Blot were used to detect the expression of DNMT1 gene and protein in human biliary tract carcinoma cell line QBC939 respectively.Results：（1） The rates of positive DNMT1 protein expression cells were（37.57±11.24） % and（10.73±6.61） % in ECC specimens and in chronic cholangeitis specimens respectively.There were significant differences between the two groups（P=0.005）;（2） The increased expression of DNMT1 protein was correlated with differentiation grade of carcinoma.The protein levels of DNMT1 were high in poorly differentiated cholangiocarcinoma,moderate in moderately differentiated cholangiocarcinoma,and low in well differentiated cholangiocarcinoma.The increased expression of DNMT1 protein was not correlated with gender,age,size of tumor,tumor location,lymph node metastasis or clinical TNM stage.（3） DNMT1 mRNA and protein were both positive in human biliary tract carcinoma cell line QBC939.Conclusions：（1） The expression level of DNMT1 protein in ECC is significantly higher than that in chronic cholangeitis tissues.The increased DNMT1 protein level is correlated with the differentiation grade of tumor and is not correlated with gender,age,tumor size,tumor location,lymph node metastasis or clinical TNM stage.This result suggests that the over-expression of DNMT1 may relate to the pathogenesis of biliary tract carcinoma and may be an early molecular event du

关 键 词：DNMT1基因 胆管肿瘤 DNA甲基化 基因表达 

分 类 号：R735.8[医药卫生—肿瘤]