人膀胱移行细胞癌HPV16/18感染与MAGE-A1基因启动子去甲基化状态的研究  

HPV16/18 Infection and MAGE-A1 Gene Promoter Methylation in Human Bladder Transitional Cell Carcinoma

作　　者：赵兴荣[1] 车团结 王锦明 陈一戎[3] 何晔[1] 

机构地区：[1]西北民族大学医学院附属医院,730030 [2]兰州百源基因技术有限公司研发中心,730000 [3]甘肃省人民医院泌尿外科,730000

出　　处：《实用癌症杂志》2009年第5期462-465,共4页The Practical Journal of Cancer

摘　　要：目的研究人膀胱移行细胞癌(BTCC)中HPV16/18感染与黑色素瘤抗原基因-A1(MAGE-A1)启动子去甲基化状态的关系。方法取40例HPV16/18阳性BTCC尿脱落细胞及HPV16/18阴性BTCC尿脱落细胞,采用甲基化特异性聚合酶链反应(Methylation-specific PCR,MSP)技术,检测BTCC中MAGE-A1基因启动子去甲基化状态,采用RT-PCR和Western blot法,分别检测其mRNA和蛋白表达水平。结果AGE-1 mRNA和蛋白表达在HPV16/18阳性BTCC和HPV16/18阴性BTCC分别为68%(17/25)、20%(3/15),2组间表达差异有统计学意义(P<0.01),不同病理分级、临床分期间其表达差异有统计学意义(P<0.05)。MAGE-A1基因在HPV16/18阴性BTCC中只有2例发生去甲基化,而在HPV16/18阳性BTCC中去甲基化发生率为52%(13/25),并且随着肿瘤分级、分期的增加,其去甲基化水平逐渐升高,差异有统计学意义(P<0.01)。结论HPV16/18感染与MAGE-A1基因启动子区去甲基化有关,能导致该基因转录表达,HPV16/18的感染可能是导致膀胱癌发生、发展的原因之一。Objective To evaluate the HPV16/18 infection and MAGE -A1 gene promoter methylation in Human bladder transitional cell carcinoma. Methods We performed methylation - specific polymerase chain reaction （ Methylation - specific PCR,MSP） to detect MAGE -A1 gene methylation status in the HPV16/18 positive and HPV16/18 negative urine exfoliated cells from 40 patients with BTCC. Reverse transcription polymerase chain reaction （RT - PCR） and Western -blot method were separately used to detect the mRNA and protein expression level. Results MAGE - 1 mRNA and protein expression in the HPV16/18 positive BTCC （68%, 17/25） were significantly higher than that in the HPV16/18 negative BTCC （20% ,3 / 15）. MAGE - 1 mRNA and protein expression were significantly different between different pathological grades and clinical stages （ P 〈 0.05 ）. Only 2 cases had MAGE - A1 gene promoter demethylation in HPV16/18 negative BTCC, whereas promoter demethylation was seen in 52% （ 13/25 ） in HPV16/18 positive BTCC. The level of demethylation was positively correlated to the pathological grades and clinical stages （ P 〈 0.01 ）. Conclusion MAGE - A1 gene promoter might relate to the HPV16/18 infection. HPV16/18 infection may play an important role in the oncogenesis and progress of BTCC.

关 键 词：膀胱移行细胞癌 甲基化 MAGE-1基因 

分 类 号：R737.14[医药卫生—肿瘤]