HTERT mRNA Partially Regulates Telomerase Activity in Gastric Adenocarcinoma and Adjacent Normal Gastric Mucosa

Abstract

The extent to which human telomerase reverse transcriptase (hTERT) mRNA and its splice variants control telomerase activity in human cancers is controversial. Telomerase and hTERT mRNA were assessed quantitatively in paired samples of gastric adenocarcinoma and adjacent normal tissue. Splice variants within the hTERT reverse transcriptase domain (alpha, beta, alphabeta) were detected by RT-PCR. In gastric adenocarcinoma, compared to normal tissue, median telomerase activity increased significantly (from 0 total product generated [tpg; 95% confidence interval CI, 0-2.3] to 16.1 tpg [95% CI, 3.7-97]; P = 0.008) and median hTERT mRNA levels also increased (from 2.21 [95% CI, 1.40-4.62] to 7.08 [95% CI, 3.26-10.8]; P = 0.0054). hTERT mRNA and telomerase activity correlated in normal gastric mucosa (r = 0.819, P = 0.0002). Alpha, beta, and alphabeta deletions were similar in both groups. We conclude that hTERT mRNA partially regulates telomerase activity in normal gastric mucosa and gastric adenocarcinoma. In contrast, hTERT mRNA splicing is not involved in the regulation of enzyme activity.