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胰腺癌组织和细胞系中DNA错配修复基因的甲基化和异常表达 被引量:1

Hypermethylation and aberrant expression of DNA mismatch repair gene in pancreatic cancer
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摘要 目的:检测错配修复基因hMLH1、hMSH2和hMLH3在胰腺癌中的甲基化和表达状态,探讨错配修复缺陷在胰腺癌发病中的作用.方法:采用甲基化特异性PCR(MSP)检测hMLH1、hMSH2和hMLH3的甲基化状态,逆转录PCR(RT-PCR)检测hMLH1、hMSH2和hMLH3的表达状态.结果:在胰腺癌组织中hMLH1、hMSH2和hMLH3的甲基化频率分别为28.6%、46.4%和39.3%;在癌旁正常组织中分别为3.6%、10.7%和12.5%,上述各基因在胰腺癌中的甲基化频率均显著高于癌旁正常组织(hMLH1:χ2=12.97,P<0.01;hMSH2:χ2=17.50,P<0.01;hMLH3:χ2=10.47,P<0.01).在胰腺癌组织中分别有25.0%、50.0%和33.9%没有检出hMLH1、hMSH2和hMLH3表达.在癌旁正常组织中分别有7.1%、8.9%和16.1%,各基因在胰腺癌中的表达缺失频率均显著高于癌旁正常组织(hMLH1:χ2=6.62,P<0.05;hMSH2:χ2=22.73,P<0.01;hMLH3:χ2=4.76,P<0.05).hMLH1在胰腺癌细胞系PANC-1和CFPAC-1检出甲基化和表达消失.hMSH2在PC-3检出甲基化和表达消失.hMLH3在PC-3和PANC-1检出甲基化和表达亦消失.结论:在胰腺癌错配修复基因缺陷较普遍参与了部分胰腺癌的发病过程. AIM: To determine the methylation and expression status of mismatch repair genes hMLH1, hMSH2 and hMLH3 and explore the role of mismatch repair defect in pancreatic cancer. METHODS: Methylation status of hMLH1, hMSH2 and hMLH3 was detected by methylation-specific polymerase chain reaction (MSP), and the expression of hMLH1, hMSH2 and hMLH3 were determined by reverse-transcription PCR (RT-PCR).RESULTS: The frequencies of methylation for hMLH1, hMSH2 and hMSH3 were 28.6%, 46.4% and 39.3%, respectively in pancreatic cancer tissues, and 3.6%, 10.7% and 12.5% in cancer-adjacent normal tissues, and there were significant differences between cancer and normal tissues (hMLHI: χ^2= 12.97, P 〈 0.01; hMSH2: χ^2 = 17.50, P 〈 0.01; hMLH3:χ^2 = 10.47, P 〈 0.01). The frequencies of expression loss for hMLH1, hMSH2 and hMSH3 were 25.0%, 50.0% and 33.9%, respectively in pancreatic cancer tissues, and 7.1%, 8.9% and 16.1% in cancer-adjacent normal tissues, and there were also marked differences between cancer and normal tissues (hMLHI: χ^2 = 6.62, P 〈 0.05; hMSH2: χ^2= 22.73, P 〈 0.01; hMLH3: χ^2 = 4.76, P 〈 0.05). Methylations of hMLH1, hMSH2 and hMLH3 were found in PANC-1, PC-3 and CF- PAC-1 cell lines, while expression loss of hMLH1 was observed in PANC-1 and CFPAC-1 cell lines, that of hMSH2 in PC-3 cell line and hMLH3 was observed in PC-3 and PANC-1 cell lines. CONCLUSION: Mismatch repair defect is common in pancreatic cancer and plays a role in pancreatic carcinogenesis.
出处 《世界华人消化杂志》 CAS 北大核心 2008年第10期1074-1077,共4页 World Chinese Journal of Digestology
基金 辽宁省教育厅高等学校科学技术研究项目 No.05L557~~
关键词 胰腺癌 甲基化 错配修复基因 聚合酶链 反应 表达缺失 Pancreatic cancer Methylation Mis-match repair gene Polymerase chain reaction Ex-pression loss
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