| Knockdown of hTERT and concurrent treatment with interferon-gamma inhibited proliferation and invasion of human glioblastoma cell lines. | |
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MedLine Citation:
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PMID: 20394835 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human telomerase reverse transcriptase (hTERT) is the catalytic component of telomerase that facilitates tumor cell invasion and proliferation. Telomerase and hTERT are remarkably upregulated in majority of cancers including glioblastoma. Interferon-gamma (IFN-gamma) modulates several cellular activities including cell cycle and multiplication through transcriptional regulation. The present investigation was designed to unravel the molecular mechanisms of the inhibition of cell proliferation, migration, and invasion of human glioblastoma SNB-19 and LN-18 cell lines after knockdown of hTERT using a plasmid vector based siRNA and concurrent treatment with IFN-gamma. We observed more than 80% inhibition of cell proliferation, migration, and invasion of both cell lines after the treatment with combination of hTERT siRNA and IFN-gamma. Our studies also showed accumulation of apoptotic cells in subG1 phase and an increase in cell population in G0/G1 with a reduction in G2/M phase indicating cell cycle arrest in G0/G1 phase for apoptosis. Semiquantitative and real-time RT-PCR analyses demonstrated significant downregulation of c-Myc and upregulation of p21 Waf1 and p27 Kip1. Western blotting confirmed the downregulation of the molecules involved in cell proliferation, migration, and invasion and also showed upregulation of cell cycle inhibitors. In conclusion, our study demonstrated that knockdown of hTERT and concurrent treatment with IFN-gamma effectively inhibited cell proliferation, migration, and invasion in glioblastoma cells through downregulation of the molecules involved in these processes and cell cycle inhibition. Therefore, the combination of hTERT siRNA and IFN-gamma offers a potential therapeutic strategy for controlling growth of human glioblastoma cells. |
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Authors:
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Joseph George; Naren L Banik; Swapan K Ray |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-04-13 |
Journal Detail:
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Title: The international journal of biochemistry & cell biology Volume: 42 ISSN: 1878-5875 ISO Abbreviation: Int. J. Biochem. Cell Biol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-02 Completed Date: 2010-09-27 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 9508482 Medline TA: Int J Biochem Cell Biol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1164-73 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29209, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Cycle
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genetics Cell Line, Tumor Cell Movement / drug effects Cell Proliferation / drug effects Cell Survival / drug effects Cyclin-Dependent Kinase Inhibitor Proteins / genetics, metabolism Down-Regulation / drug effects Gene Expression Regulation, Neoplastic / drug effects Gene Knockdown Techniques* Glioblastoma / enzymology*, genetics, pathology* Humans Interferon-gamma / pharmacology* Neoplasm Invasiveness RNA, Messenger / genetics, metabolism RNA, Small Interfering / metabolism Telomerase / genetics, metabolism* Transcription, Genetic / drug effects Transfection Tumor Stem Cell Assay Up-Regulation / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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NS57811/NS/NINDS NIH HHS; R01 CA091460-06/CA/NCI NIH HHS; R01 CA91460/CA/NCI NIH HHS; R01 NS057811-04/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclin-Dependent Kinase Inhibitor Proteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 82115-62-6/Interferon-gamma; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase |
| Comments/Corrections | |
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