Protection of telomeres 1 protein levels are associated with telomere length in gastric cancer

Abstract

Protection of telomeres 1 (Pot1) is a telomere-associated protein, which binds to the single-stranded DNA extensions of telomeres and regulates telomere length. Pot1 production was examined and compared with telomere length in gastric cancer. Pot1 production and telomere lengths were assessed in 5 human gastric cancer cell lines by immunoblotting and Southern blotting, respectively. Pot1 intracellular localization was examined with protein fractionation. Pot1 index and telomere volume were examined in human gastric mucosa and cancer by immunohistochemistry and in situ hybridization. Pot1 protein levels, which were lower than those in the lymphocytes of healthy persons, were significantly correlated with telomere length in gastric cancer cells (P=0.0167). Pot1 protein was mainly detected in the nuclear fraction and increased by G2/M blocking with nocodazole in MKN28 cells. Pot1 indexes were correlated with telomere volumes in gastric cancers (P<0.0001). Pot1 index was decreased in gastric epithelia distant from cancer (84±14%), in peritumoral epithelia (72±24%), and in stage I-II (39±14%) and stage III-IV (23±14%) gastric cancers (P<0.0001). Pot1 index was lower in stage III-IV than in stage I-II gastric cancers (P<0.05). Pot1-low cases showed advanced cancer invasion (P<0.05). Thus, Pot1 production was closely associated with telomere length in gastric mucosa and cancers. Pot1 might be a good in situ marker for the examination of cell-specific telomere length.