Telomere stability is believed to be related to aging and tumorigenesis. Besides telomerase, telomere length is also regulated by several telomere-specific binding proteins. Tankyrase 1, a telomeric poly(ADP-ribose) polymerase (PARP), elongates telomere length by inhibiting TRF1 binding to telomeres. In order to study the synergistic action of tankyrase 1 and telomerase in the maintenance of telomere length in mammalian cells, we constructed antisense tankyrase 1 (aTNKS) eukaryotic expression

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... ctors and then transfected them into the SGC-7901 human gastric cancer cell line, as well as SGC-7901 cells that had been transfected with antisense hTR (7901-ahTR) and antisense hTERT (7901-ahTERT) with DOTAP liposomes. The activity of telomerase, telomere length and telomerase-associated protein activities were measure by TRAP-ELISA, Southern blot and Western blot analysis, respectively, in aTNKS transfected and untransfected cells. The results demonstrated that telomere length was significantly shorter in cells with concomitant tankyrase 1 and telomerase inhibition than by either tankyrase 1 or telomerase inhibition alone, in SGC-7901 cells. We also found that aTNKS had no effect on telomerase activity. These results reveal that inhibition of tankyrase 1 could shorten telomere length and play a synergistic role with telomerase inhibitors in telomere length shortening in the SGC-7901 gastric cancer cell line. Co-inhibition of tankyrase 1 and telomerase activity may be a rational strategy for telomere-directed gastric cancer therapeutics. Abbreviations: hTERT, human telomerase reverse transcriptase; hTR, human telomerase RNA; TP1, human telomerase associated protein 1; TRF, terminal restriction fragment; TRAP, telomeric repeat amplification protocol