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非小细胞肺癌中hMLH1启动子的甲基化

Methylation of Promoter for hMLH1 in Non-small Cell Lung Cancer

  • 摘要: 目的 探讨在非小细胞肺癌(NSCLC)中DNA修复基因hMLH1启动子甲基化与基因转录失活的关系,观察5-Aza-CAR的干预作用。方法 甲基化特异的PCR(methyl-specific PCR,MSP)和RT-PCR法分别测定基因的甲基化率和转录水平。结果 NSCLC癌/癌旁组织中的甲基化率分别是hMLH1为55%和14%;〉65岁组hMLH1甲基化率明显高于≤65岁组(P〈0.01),hMLH1甲基化率随吸烟指数增高而升高(P〈0.05或P〈0.01);hMLH1的甲基化率随TNM临床分期进展而逐渐增加(P〈0.05或P〈0.01)。甲基化的NSCLC标本hMLH1基因mRNA转录下降或失活,在细胞株水平5-Aza-CdR处理后hMLH1恢复转录活性。结论 启动子甲基化是调节hMLH1转录活性的重要机制,5-Aza-CDR具有逆转甲基化而恢复转录的作用。

     

    Abstract: Objective  To understand the role of promoter methylation for hML H1 in non-small cell lung cancer. Methods  The methylation status was determined by MSP (methyl-specific PCR), and RT-PCR was employed to measure mRNA level. Results  The f requencies of methylation in NSCLC and corresponding non-neoplastic lung tissues were : 55 % and 14 % for hML H1. Methylation of hML H1 was more frequent in > 65 group ( P < 0. 01) . Methylation of hML H1 was more frequent in smoking group ( ( P <0. 05 or P < 0. 01) . Methylation of hML H1 was more f requent with TNM stage advanced ( P < 0. 05 or P< 0. 01) . The samples with methylated status showed the decline or loss of hML H1 mRNA t ranscription. 5-Aza-CdR could induce re-expression of the silenced methylated hML H1. Conclusion  Promoter methylation is the predominant mechanism in hML H1 deregulation in NSCLC,but 5-Aza-CdR could reverse the gene transcriptional activity.

     

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