Positive Regulation of Human Telomerase Reverse Transcriptase Gene Expression and Telomerase Activity by DNA Methylation in Pancreatic Cancer
Positive Regulation of Human Telomerase Reverse Transcriptase Gene Expression and Telomerase Activity by DNA Methylation in Pancreatic Cancer
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DOI：
10.1245/s10434-009-0333-8
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发表时间：
2009-04-01
影响因子：
3.7
通讯作者：
Wig, Jai Dev
中科院分区：
文献类型：
--
作者：
Kumari, Alpana;Srinivasan, Radhika;Wig, Jai Dev
我们试图确定端粒酶及其催化亚基hTERT在胰腺癌中的作用，并通过启动子甲基化评估hTERT的表观遗传调控。采用逆转录聚合酶链反应、端粒重复序列扩增法和甲基化特异性聚合酶链反应分别检测胰腺癌组织中hTERT的表达、端粒酶活性和基因启动子甲基化状态。hTERT表达与端粒酶活性相关（P <0.05），与hTERT启动子甲基化（P <0.001）和p16启动子甲基化正相关。单因素和多因素分析显示hTERT表达和端粒酶活性均为预后不良的危险因素（P <0.05），hTERT表达和端粒酶活性是胰腺癌预后不良的预测因子。hTERT基因表达受启动子甲基化正调控。
We sought to determine the role of telomerase and its catalytic subunit hTERT in pancreatic cancer and evaluate the epigenetic regulation of hTERT by promoter methylation.Thirty paired samples of pancreatic ductal adenocarcinomas and adjacent normal tissue and 12 chronic pancreatitis samples were studied. Reverse transcriptase polymerase chain reaction, telomeric repeat amplification protocol assay, and methylation-specific polymerase chain reaction were performed to analyze hTERT expression, telomerase activity, and methylation status of gene promoters, respectively.hTERT and telomerase activity were upregulated in pancreatic cancer compared with paired normal tissues and samples of pancreatitis. hTERT expression correlated with telomerase activity (P < .05) and in turn correlated positively with hTERT promoter methylation (P < .001) and p16 promoter methylation. hTERT transcript expression and telomerase activity both conferred a worse outcome by univariate and multivariate analysis (P < .05).hTERT expression and telomerase activity are predictors of poor outcome in pancreatic cancer. hTERT gene expression is positively regulated by promoter methylation.