| HIV-Tat-mediated delivery of an LPTS functional fragment inhibits telomerase activity and tumorigenicity of hepatoma cells. | |
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MedLine Citation:
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PMID: 20816839 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-20 |
Journal Detail:
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Title: Gastroenterology Volume: 140 ISSN: 1528-0012 ISO Abbreviation: Gastroenterology Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-21 Completed Date: 2011-01-20 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0374630 Medline TA: Gastroenterology Country: United States |
Other Details:
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Languages: eng Pagination: 332-43 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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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. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carcinoma, Hepatocellular / drug therapy* Drug Delivery Systems Humans Liver Neoplasms / drug therapy* Mice 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 |
| Chemical | |
Reg. No./Substance:
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0/PINX1 protein, human; 0/Recombinant Fusion Proteins; 0/Tumor Suppressor Proteins; 0/tat Gene Products, Human Immunodeficiency Virus; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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