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

Ann Surg Oncol. 2009 Apr;16(4):1051-9. doi: 10.1245/s10434-009-0333-8. Epub 2009 Feb 5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • DNA Methylation*
  • Epigenesis, Genetic
  • Gene Expression
  • Gene Expression Regulation
  • Genes, p16
  • Humans
  • Middle Aged
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatitis, Chronic / genetics
  • Telomerase / genetics*
  • Telomerase / metabolism

Substances

  • TERT protein, human
  • Telomerase