Expression of telomeric repeat binding factor 1 and 2 and TRF1-interacting nuclear protein 2 in human gastric carcinomas

Abstract

Telomeric repeat binding factor 1 (TRF1) and 2 (TRF2) may play key roles in the maintenance of telomere function. TRF1 negatively regulates telomere elongation, while TRF2 protects the chromosome ends by inhibiting end-to-end fusions. We examined the expression of TRF1 and TRF2 in 20 gastric carcinomas by reverse transcription polymerase chain reaction and then analyzed the relation with telomerase activity and other telomerase components such as human telomerase reverse transcriptase (TERT), human telomerase RNA component (hTR), human telomerase-associated protein (TEP1) and TRF1-interacting, ankyrin-related ADP-ribose polymerase (tankyrase) as well as TRF1-interacting nuclear protein 2 (TIN2). Of 20 gastric carcinomas examined, 10 (50%) and 12 (60%) expressed TRF1 and TRF2 at higher levels than did non-neoplastic mucosa, respectively. No obvious correlation was observed between TRF1 expression and telomerase activity or expression of TERT, hTR and TEP1. Carcinomas with high TRF1 expression expressed significantly higher levels of tankyrase and TIN2 than did those with low TRF2 expression (p<0.05). The telomerase activities and the levels of TERT, hTR and TEP1 showed tendency to be lower in tumors expressing TRF1 at low levels, although it was not significant. On the other hand, carcinomas with short telomere length (shorter than 2 Kbp) expressed significantly stronger telomerase activities and higher TRF1 expression (p<0.05) and tended to express TRF2 and TIN2 at higher levels than those with long telomere length. The results suggest that gastric carcinomas with short telomeres need high levels of telomerase activity and large quantity of TRFs and TIN2, whereas those with long telomeres do not require high levels of telomerase activity and telomere associated proteins.