Positive regulation of human telomerase reverse transcriptase gene expression and telomerase activity by DNA methylation in pancreatic cancer.

AIM: 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. METHODS: 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. RESULT: 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). CONCLUSION: hTERT expression and telomerase activity are predictors of poor outcome in pancreatic cancer. hTERT gene expression is positively regulated by promoter methylation.