Document Detail

HIV-Tat-mediated delivery of an LPTS functional fragment inhibits telomerase activity and tumorigenicity of hepatoma cells.
MedLine Citation:
PMID:  20816839     Owner:  NLM     Status:  MEDLINE    
BACKGROUND & AIMS: Human liver-related putative tumor suppressor (LPTS) is a gene that encodes a telomerase inhibitory protein that is similar to human Pin2/TRF1-interacting protein. The LPTS protein binds directly to the telomerase catalytic subunit (human telomerase reverse transcriptase) and suppresses telomerase activity. Telomere maintenance and telomerase activity are required for long-term proliferation of cancer cells, so LPTS might be used in anticancer strategies.
METHODS: The carboxy-terminal (functional) fragment of LPTS was fused to the transactivator of transcription of human immunodeficiency virus (Tat)-an 11-amino acid peptide that translocates across the cell membrane; the TAT-fused C-terminal of LPTS (TAT-LPTS-LC) was purified and transduced into cells. Telomerase activity was identified by using the telomeric repeat amplification protocol. The effects of the TAT-LPTS-LC protein on cell proliferation and death were evaluated by colorimetric tetrazolium salt and flow cytometry analyses. Tumor growth was analyzed in nude mice.
RESULTS: The purified TAT-LPTS-LC protein was efficiently delivered into the cells, where it suppressed telomerase activity and shortened telomere length. TAT-LPTS-LC inhibited proliferation of telomerase-positive hepatocellular carcinoma BEL-7404 and hepatoblastoma HepG2cells and induced their death; however, it had no effect on telomerase-negative liver cell line L02 and osteosarcoma cell line Saos-2. In mice, tumor formations by BEL-7404 cells were suppressed by TAT-LPTS-LC treatments.
CONCLUSIONS: Transduction of hepatoma cells with a fusion protein that contains the C-terminal, functional fragment of LPTS and human immunodeficiency virus Tat (TAT-LPTS-LC) causes telomere shortening, limits proliferation, and inhibits growth of tumors from these cells in mice. TAT-LPTS-LC inhibits telomerase activity and might be developed as an anticancer agent.
Guangming Chen; Liang Da; Hongfei Wang; Ying Xu; Guoyuan Chen; Chengfu Sun; Leiming Wang; Jing Zhao; Fang Zhang; Jian Feng; Yifei Wang; Pierre Tiollais; Tsaiping Li; Mujun Zhao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-20
Journal Detail:
Title:  Gastroenterology     Volume:  140     ISSN:  1528-0012     ISO Abbreviation:  Gastroenterology     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-21     Completed Date:  2011-01-20     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  332-43     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
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MeSH Terms
Carcinoma, Hepatocellular / drug therapy*
Drug Delivery Systems
Liver Neoplasms / drug therapy*
Mice, Nude
Recombinant Fusion Proteins / administration & dosage*,  genetics,  metabolism
Telomerase / antagonists & inhibitors*
Tumor Suppressor Proteins / administration & dosage*,  genetics,  metabolism
tat Gene Products, Human Immunodeficiency Virus / administration & dosage*,  genetics,  metabolism
Reg. No./Substance:
0/PINX1 protein, human; 0/Recombinant Fusion Proteins; 0/Tumor Suppressor Proteins; 0/tat Gene Products, Human Immunodeficiency Virus; EC

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