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磷酸酶基因CpG岛甲基化状态及其在膀胱移行细胞癌中的表达

CpG island methylation status of phosphatase and tension homology deleted on chromosome ten gene and its expression in bladder transitional cell carcinoma

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【作者】 张志华郭柏鸿车团结史葆光黄贤德李元陈一戎

【Author】 ZHANG Zhi-hua~1,Guo Bai-hong~1,CHE Tuan-jie~2,SHI Bao-guang~1, HUANG Xian-de~1,LI Yuan~1,CHEN Yi-rong~1 (1.Department of Urology,People’s Hospital of Gansu Province,Lanzhou 730000,China;2.School of Life Sciences,Lanzhou University,Lanzhou 730000,China)

【机构】 甘肃省人民医院泌尿外科兰州大学生命科学学院

【摘要】 目的探讨磷酸酶基因(PTEN)CpG岛甲基化状态及其在膀胱移行细胞癌(BTCC)中的表达。方法应用甲基化特异性聚合酶链式反应检测32例BTCC和癌旁正常组织标本中PTEN基因启动子区甲基化状态,逆转录聚合酶链式反应和蛋白印迹法检测其mRNA和蛋白表达水平。结果PTEN基因在BTCC组织中甲基化率为65.6%,随着肿瘤分级、分期的增加,甲基化水平逐渐升高,而在正常膀胱组织中未发现甲基化。PTEN mRNA和蛋白表达在正常组织和BTCC组织中分别为93.8%、62.5%和15.6%、6.3%,差异有统计学意义(P<0.01)。在21例启动子异常甲基化的BTCC组织标本中,19例伴有PTEN基因表达缺失或下调,两者之间存在明显负相关(r=-0.564,P<0.01)。结论PTEN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,是膀胱癌发生、发展的原因之一。

【Abstract】 Objective To detect hypermethylation status of the 5’CpG island locating in the promoter region of phosphatase and tension homology deleted on chromosome ten(PTEN) gene and the expression level of its mRNA and protein in bladder transitional cell carcinoma(BTCC). Methods Methylation-specific PCR(MSP) technique was used to detect methylation status of PTEN gene in 32 samples of the BTCC tissues and normal tissues,and to detect their mRNA and protein expression levels by RT-PCR and Western blot method.Results The frequency of promoter methylation of PTEN gene was 65.6%in BTCC tissues,but it was not found in normal bladder tissues.The frequency of promoter methylation increased with the increase of tumor grade and stage.The expression of PTEN mRNA and protein in the normal bladder tissues and BTCC tissues were 93.8%,62.5%and 15.6%,6.3%(P<0.01) respectively.Among 21 patients with the aberrant promoter methylation,19 patients showed the loss of the expression of PTEN gene and there was a significant negative correlation between them(r=-0.564,P<0.01). Conclusion Hypermethylation can inactivate the transcription of PTEN and reduce its protein expression.It may be a considerable mechanism which leads to oncogenesis,metastasis of BTCC.

【基金】 兰州市科技计划资助项目(05-2-14)
  • 【文献出处】 兰州大学学报(医学版) ,Journal of Lanzhou University(Medical Sciences) , 编辑部邮箱 ,2009年04期
  • 【分类号】R737.14
  • 【被引频次】2
  • 【下载频次】56
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