Inhibition of tankyrase 1 in human gastric cancer cells enhances telomere shortening by telomerase inhibitors

  • Authors:
    • Hao Zhang
    • Meng-Hua Yang
    • Jing-Jing Zhao
    • Ling Chen
    • Song-Tao Yu
    • Xu-Dong Tang
    • Dian-Chun Fang
    • Shi-Ming Yang
  • View Affiliations

  • Published online on: October 1, 2010     https://doi.org/10.3892/or_00000955
  • Pages: 1059-1065
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Abstract

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 anti-sense tankyrase 1 (aTNKS) eukaryotic expression vectors 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.

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October 2010
Volume 24 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhang H, Yang M, Zhao J, Chen L, Yu S, Tang X, Fang D and Yang S: Inhibition of tankyrase 1 in human gastric cancer cells enhances telomere shortening by telomerase inhibitors . Oncol Rep 24: 1059-1065, 2010
APA
Zhang, H., Yang, M., Zhao, J., Chen, L., Yu, S., Tang, X. ... Yang, S. (2010). Inhibition of tankyrase 1 in human gastric cancer cells enhances telomere shortening by telomerase inhibitors . Oncology Reports, 24, 1059-1065. https://doi.org/10.3892/or_00000955
MLA
Zhang, H., Yang, M., Zhao, J., Chen, L., Yu, S., Tang, X., Fang, D., Yang, S."Inhibition of tankyrase 1 in human gastric cancer cells enhances telomere shortening by telomerase inhibitors ". Oncology Reports 24.4 (2010): 1059-1065.
Chicago
Zhang, H., Yang, M., Zhao, J., Chen, L., Yu, S., Tang, X., Fang, D., Yang, S."Inhibition of tankyrase 1 in human gastric cancer cells enhances telomere shortening by telomerase inhibitors ". Oncology Reports 24, no. 4 (2010): 1059-1065. https://doi.org/10.3892/or_00000955