Telomerase is active in normal gastrointestinal mucosa and not up-regulated in precancerous lesions

Telomerase is a ribonucleoprotein complex which, by de novo synthesized tel omeric TTAGGG repeats, prevents telomere erosion. While telomerase is activ e in most cancers, conflicting results exist for normal tissues and premali gnant lesions. To establish the telomerase status of normal gastrointestina l mucosa and to elucidate whether telomerase up-regulation is an early or l ate event in carcinogenesis, we determined the telomerase activity of 88 bi opsies of normal mucosa from esophagus, stomach, and intestine and compared it with that of 21 samples of premalignant lesions and 6 adenocarcinomas u sing the telomere-repeat amplification protocol assay. Telomerase was found in all normal tissues, revealing most activity in esophagus (11 samples), followed by intestine (45 samples), and stomach (32 samples). In 53% of the stomach samples, enzyme activity could only be demonstrated when telomeras e inhibitors were eliminated by a modified telomerase assay. In the 21 prec ancerous lesions (5 Barrett's esophagus, 3 stomach intestinal metaplasias, and 13 colorectal adenomas of type I/II dysplasia) a similar or even reduce d telomerase activity was seen, while the adenocarcinomas showed high activ ity. These data demonstrate that telomerase activity is expressed in all ep ithelia along the gastrointestinal tract, thus confirming our previous hypo thesis that telomerase is constitutively expressed in permanently renewing epithelia. Furthermore, activity was not increased in preneoplastic lesions , suggesting that telomerase up-regulation is a late event during carcinoge nesis of the esophagus, stomach, and intestine.