Telomere length and telomerase activity in carcinogenesis of the stomach

Telomerase activity is generally absent in primary cell cultures and normaltissues. Telomerase is known to be induced upon immortalization ormalignant transformation of human cells. In the present study, we analyzedboth telomere length and telomerase activity in biopsy samples from mucosaundergoing metaplasia, adenoma and cancer of the stomach. We attempted toestimate the correlation between telomerase activity and telomere length inthese tissues. Telomerase activity was estimated using the telomeric repeatamplification protocol and telomere length by Southern blot analysis.Extracts were defined as telomerase-negative when the signals were lessintense than those for 10(2) KATO-III cells (positive control). We detectedtelomerase activity in 15%, 45% and 89% of the examined cases of intestinalmetaplasia, adenoma and gastric cancer respectively. However, telomerelength in the gastric mucosa became reduced as the mucosa underwentmetaplasia and developed into adenoma. Gastric cancers showed a broad rangeof telomere length among cases. However, gastric adenomas showed theshortest telomere length. These results suggest that telomerase isexpressed during the early phase (intestinal metaplasia through adenoma) ofgastric carcinogenesis, although the activity at that stage is not highenough to fully restore the reduced telomeric DNA.