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Telomerase activity and expression of human telomerase catalytic subunit gene in esophageal tissues
Tatsuro Tominaga1, Hiromasa Kashimura, Kaori Suzuki
1Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Japan.
Background:
Telomerase, the ribonucleoprotein enzyme that synthesizes telomeric DNA, is thought to be necessary for cellular immortality and carcinogenesis. Telomerase activity is associated with the majority of malignant human cancers. The mRNA that encodes the telomerase catalytic subunit (human telomerase repeat transcriptase; hTERT) has recently been identified, and the expression of the hTERT gene is thought to regulate the activation of telomerase. However, the expression of hTERT mRNA in esophageal tissues has not been reported. We investigated hTERT gene expression in cancerous and noncancerous esophageal tissues, and determined the relationship between hTERT mRNA expression and telomerase activity.
Methods:
Tissues from esophageal carcinomas in 14 patients, reflux esophagitis in 12 patients, esophageal acanthosis in 2 patients, esophageal papilloma in 1 patient, radiation esophagitis in 1 patient, and normal esophageal epithelium in 11 patients (including 3 specimens of normal epithelium from patients with esophageal carcinoma) were examined. All specimens were taken endoscopically. hTERT gene expression was investigated using reverse transcription-polymerase chain reaction (RT-PCR). Quantitative analysis of telomerase activity was analyzed by fluorescence telomeric repeat amplification protocol (F-TRAP) assay.
Results:
Thirteen of the 14 (93%) esophageal carcinoma specimens expressed hTERT mRNA and revealed detectable telomerase activity. Noncancerous esophageal lesions had not only hTERT mRNA expression with a high frequency (14 of 16 cases; 88%) but also detectable telomerase activity (12 of 13 cases; 92%). Normal esophageal epithelium also highly expressed hTERT mRNA (10 of 11 cases; 91%) and revealed detectable telomerase activity (all 9 cases; 100%). In 32 of the 35 specimens analyzed for both hTERT mRNA and telomerase activity (91%), the expression of hTERT mRNA was consistent with detectable telomerase activity.
Conclusions:
The expression of hTERT mRNA was detected not only in cancerous but also in noncancerous esophageal tissues at a high frequency. This result was different from that reported for other gastrointestinal epithelium. Moreover, telomerase activity in esophageal carcinoma was significantly stronger than that in reflux esophagitis and normal epithelium. In addition, there was a strong relation ship between the detection of telomerase activity and the expression of hTERT mRNA in cancerous and noncancerous esophageal tissues. Thus, the qualitative analysis of hTERT mRNA expression may not be useful as a biomarker of carcinoma in esophageal tissues. Nevertheless, the quantitative analysis of telomerase activity may be somewhat useful.