RUNX3基因启动子甲基化与膀胱移行细胞癌发生的关系  

Studying the Expression of RUNX3 gene and Its CpG Island Methylation Status in Bladder transitional Cell Carcinoma

作　　者：张志华[1] 郭柏鸿[1] 车团结[1] 史葆光[1] 陈一戎[1] 

机构地区：[1]甘肃省人民医院泌尿外科,兰州730000

出　　处：《国际泌尿系统杂志》2009年第3期296-300,共5页International Journal of Urology and Nephrology

基　　金：甘肃省兰州市科技计划项目资助（05-2-14）

摘　　要：目的检测抑癌基因RUNX3启动子区CpG岛甲基化状态及其在BTCC中mRNA和蛋白表达水平。方法应用甲基化特异性聚合酶链反应（Methylation—specific PCR，MSP）技术检测BTCC中RUNX3基因启动子区域甲基化状态，RT—PCR和Western blot法分别检测其mRNA和蛋白表达水平。结果RUNX3基因在正常膀胱组织中未发生甲基化，而在BTCC组织中甲基化频率占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，差异有统计学意义（P〈0．01）。在15例启动子异常甲基化的癌组织标本中，14例同时伴有RUNX3基因表达缺失或下调，二者存在明显的相关性（r=0．6472。P=0．012）。RUNX3 mRNA和蛋白表达在正常膀胱组织和BTCC组织分别为93．8％（30／32）、34．4％（11／32），二组间表达差异有统计学意义（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RUNX3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，这可能是导致膀胱癌发生和转移的原因之一。Objectives To detect hypermethylation status of the 5＇ CpG island locating in the promoter region of RUNX3 gene and the expression level of their mRNA and protein in bladder transitional cell carcinoma （nrcc）. Methods Using methylation - specific PCR （MSP） technique to detect methylation status of RUNX3 gene in BTCC, and to detect their mRNA and protein expression level by RT - PCR and Western blot method. Results The frequence of Promoter methylation of RUNX3 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 （ p 〈0.01 ）. In 15 patients with the aberrant Promoter methylation, 14 patients shown the loss expression of RUNX3 gene （r=0.6472, p =0. 012）. The expression of RUNX3 mRNA and protein in the normal bladder tissues and BTCC tissue were 93.8 % （ 30/32 ）, 34.4 % （ 11/32 ）, respectively （ p 〈 0.01 ）. It was currelated with its clinical stages and pathological grades （ p 〈 0.05 ）. Conclusions Hypermethylation can inactivate the transcription of RUNX3 and reduce its protein expression. It may be a considerable mechanism which leads to oneogenesis, metastasis of BTCC.

关 键 词：癌 移行性细胞 膀胱肿瘤 操纵子 甲基化 

分 类 号：R737.14[医药卫生—肿瘤]