| Inhibition of tankyrase 1 in human gastric cancer cells enhances telomere shortening by telomerase inhibitors. | |
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MedLine Citation:
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PMID: 20811689 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Hao Zhang; Meng-Hua Yang; Jing-Jing Zhao; Ling Chen; Song-Tao Yu; Xu-Dong Tang; Dian-Chun Fang; Shi-Ming Yang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oncology reports Volume: 24 ISSN: 1791-2431 ISO Abbreviation: Oncol. Rep. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-02 Completed Date: 2011-01-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9422756 Medline TA: Oncol Rep Country: Greece |
Other Details:
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Languages: eng Pagination: 1059-65 Citation Subset: IM |
Affiliation:
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Institute of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Southern Blotting, Western Cell Line, Tumor Enzyme Inhibitors / pharmacology Enzyme-Linked Immunosorbent Assay Humans Reverse Transcriptase Polymerase Chain Reaction Stomach Neoplasms / enzymology*, genetics* Tankyrases / metabolism* Telomerase / metabolism* Telomere / drug effects, metabolism* Transfection |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; EC 2.4.2.30/Tankyrases; EC 2.4.4.30/TNKS protein, human; EC 2.7.7.49/Telomerase |
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