膀胱移行细胞癌患者RASSF1A蛋白表达和启动子区甲基化的研究

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目的:探讨RASSF1A(RAS association domain family1A)蛋白表达水平与启动子甲基化的关系。方法:应用免疫印迹技术(western-blot)检测10例正常膀胱组织和23例膀胱移行细胞癌(Badder transitional cell carcinoma,BTCC)组织中RASSF1A蛋白表达水平;用甲基化特异性PCR(Methylation-Specific PCR,MSP)方法检测正常膀胱组织,BTCC组织中RASSF1A基因启动子CPG岛甲基化状态。结果:RASSF1A蛋白在正常膀胱组织中全部表达,在BTCC组织中表达率为30.4(7/23),二组间表达差异有统计学意义(P<0.05),但各肿瘤分期、病理分级间的表达差异无统计学意义(P>0.05)。在正常膀胱组织中,RASSF1A基因启动子未发生甲基化;在BTCC组织中,RASSF1A基因启动子甲基化频率为60.9(14/23),二组间表达差异有统计学意义(P<0.05)。在14份启动子异常甲基化的BTCC标本中,13份同时伴有RASSF1A蛋白表达缺失或下调,两者存在明显相关性(P<0.05)。结论:RASSF1A基因启动子在BTCC组织中发生异常甲基化,使RASSF1A蛋白表达缺失,推测RASSF1A基因启动子CPG岛异常甲基化导致RASSF1A基因失活从而引起肿瘤的发生,而与肿瘤的进展可能无关。 Objective: To investigate the relationship between RAS association domain family1A protein expression and promoter methylation. Methods: Western blot was used to detect the expression of RASSF1A protein in 10 normal bladder tissues and 23 BTCC tissues. Methylation-specific PCR (Methylation-Specific PCR) PCR, MSP) were used to detect the methylation status of RASSF1A promoter CPG island in normal bladder tissues and BTCC tissues. Results: The expression of RASSF1A protein was all in normal bladder tissue, and the expression rate was 30.4 (7/23) in BTCC tissues. There was significant difference between the two groups (P <0.05) The difference was not statistically significant (P> 0.05). In normal bladder tissue, the promoter of RASSF1A gene was not methylated. The promoter methylation frequency of RASSF1A gene was 60.9 (14/23) in BTCC tissues, with significant difference between the two groups (P <0.05 ). Of the 14 BTCC specimens with abnormal promoter methylation, 13 were associated with the loss or downregulation of RASSF1A protein expression (P <0.05). CONCLUSIONS: RASSF1A promoter is aberrantly methylated in BTCC tissues, and the expression of RASSF1A protein is absent. It is speculated that aberrant methylation of RASSF1A promoter CPG island leads to the inactivation of RASSF1A gene, which may lead to tumor development. However, Nothing to do
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