TMS1/ASC基因CpG岛甲基化与膀胱移行细胞癌发生的关系  

Expression of TMS1/ASC Gene and its CpG Island Methylation Status in Transitional Cell Carcinoma of Bladder

作　　者：张志华[1] 郭柏鸿[1] 车团结[2] 郭利君[1] 王锦明[2] 李元[1] 陈一戎[1] 

机构地区：[1]甘肃省人民医院泌尿外科,730000 [2]兰州大学生命科学学院,730000

出　　处：《实用癌症杂志》2009年第4期341-344,共4页The Practical Journal of Cancer

基　　金：甘肃省兰州市科技发展计划基金资助项目(05-2-14)

摘　　要：目的检测抑癌基因TMS1/ASC启动子区5′CpG岛甲基化状态及其在膀胱移行细胞癌(BTCC)中mRNA和蛋白表达水平。方法应用MSP技术检测膀胱移行细胞癌中TMS1/ASC基因启动子区甲基化状态,RT-PCR和Western blot法分别检测其mRNA和蛋白表达水平。结果TMS1/ASC基因在正常膀胱组织中未发生甲基化,而在癌组织中甲基化频率为46.9%(15/32),并且随着肿瘤分级、分期的增加,其甲基化水平逐渐升高(χ2=23.106,P<0.05)。在15例启动子异常甲基化的BTCC标本中,14例同时伴有TMS1/ASC基因表达缺失或下调,两者存在明显的相关性(γ=0.5842,P<0.05)。TMS1/ASC mRNA和蛋白表达在正常膀胱组织和BTCC组织中分别为81.3%(26/32)、18.8%(6/32)(P<0.01),不同病理分级、临床分期间差异有统计学意义(P<0.05)。结论TMS1/ASC基因启动子区异常甲基化可能导致该基因转录表达失活,使其mRNA和蛋白表达减少,甚至缺失,这可能是膀胱癌发生、发展的原因之一。Objective To detect methylation status of the 5＇ CpG island locating in the promoter region of TMS1/ASC gene and the expression level of their mRNA and protein in transitional cell carcinoma of the bladder （BTCC）. Methods Using methylation - specific PCR （MSP） technique to detect methylation status of TMS1/ASC gene in BTCC ,and to detect their mRNA and protein expression level by RT - PCR and Western blot methods. Results The frequenee of promoter methylation of TMS1/ ASC gene was 46.9 % （ 15/32 ） in BTCC tissues, but it was not found in normal bladder tissues. The frequence of promoter methylation was increased with the increasing tumor grade and stage （χ^2 = 23. 106, P 〈 0.05 ）. In 15 patients with the aberrant promoter methylation, 14 patients showed the loss expression of TMS1/ASC gene, a significant correlation was observed in them （γ= 0. 5842 ,P 〈 0.05 ）. The expression of TMS1/ASC mRNA and protein in the normal bladder tissues and BTCC tissue were 81.3% （26/32） ,18.8% （6/32）, respectively （P 〈 0.01 ）. It was correlated with its clinical stages and pathological grades （P 〈 0.05）. Conclusion Hypermethylation can inactivate the transcription of TMS1/ASC and reduce its mRNA and protein expression. It may be a considerable mechanism that leads to oncogenesis,metastasis of BTCC.

关 键 词：膀胱移行细胞癌 DNA甲基化 TMS1/ASC基因 

分 类 号：R737.14[医药卫生—肿瘤]