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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 4/2009

01-04-2009 | Laboratory and Translational Research

Positive Regulation of Human Telomerase Reverse Transcriptase Gene Expression and Telomerase Activity by DNA Methylation in Pancreatic Cancer

Authors: Alpana Kumari, PhD, Radhika Srinivasan, MD, PhD, Rakesh Kumar Vasishta, MD, Jai Dev Wig, MD

Published in: Annals of Surgical Oncology | Issue 4/2009

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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.
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Metadata
Title
Positive Regulation of Human Telomerase Reverse Transcriptase Gene Expression and Telomerase Activity by DNA Methylation in Pancreatic Cancer
Authors
Alpana Kumari, PhD
Radhika Srinivasan, MD, PhD
Rakesh Kumar Vasishta, MD
Jai Dev Wig, MD
Publication date
01-04-2009
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 4/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0333-8

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