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Annals of Surgical Oncology

, Volume 16, Issue 4, pp 1051–1059 | Cite as

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

  • Alpana Kumari
  • Radhika Srinivasan
  • Rakesh Kumar Vasishta
  • Jai Dev Wig
Laboratory and Translational Research

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.

Keywords

Pancreatic Cancer Chronic Pancreatitis Promoter Methylation Pancreatic Ductal Adenocarcinoma hTERT mRNA 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

A.K. was supported by Council of Scientific and Industrial Research, New Delhi, India in the form of fellowship, grant 9/141(154)-EMR-2003.

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Copyright information

© Society of Surgical Oncology 2009

Authors and Affiliations

  • Alpana Kumari
    • 1
  • Radhika Srinivasan
    • 2
  • Rakesh Kumar Vasishta
    • 3
  • Jai Dev Wig
    • 1
  1. 1.Department of General SurgeryPostgraduate Institute of Medical Education and ResearchChandigarhIndia
  2. 2.Department of Cytology and Gynecological PathologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
  3. 3.Department of HistopathologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia

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