Document Detail


Inhibition of tankyrase 1 in human gastric cancer cells enhances telomere shortening by telomerase inhibitors.
MedLine Citation:
PMID:  20811689     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncology reports     Volume:  24     ISSN:  1791-2431     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-02     Completed Date:  2011-01-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1059-65     Citation Subset:  IM    
Affiliation:
Institute of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
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MeSH Terms
Descriptor/Qualifier:
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:
0/Enzyme Inhibitors; EC 2.4.2.30/Tankyrases; EC 2.4.4.30/TNKS protein, human; EC 2.7.7.49/Telomerase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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