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


RESULTS
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).


CONCLUSIONS
hTERT expression and telomerase activity are predictors of poor outcome in pancreatic cancer. hTERT gene expression is positively regulated by promoter methylation.
Kumari
Alpana
A
Department of General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Srinivasan
Radhika
R
Vasishta
Rakesh Kumar
RK
Wig
Jai Dev
JD
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015870:Gene Expression; D005786:Gene Expression Regulation; D019942:Genes, p16; D006801:Humans; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D050500:Pancreatitis, Chronic / Q000235:genetics; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism
C509186:TERT protein, human; D019098:Telomerase