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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2010-3-3
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pubmed:abstractText |
Stereospecific radiation treatment offers a distinct opportunity for temporal and spatial regulation of gene expression at tumor sites by means of inducible promoters. To this end, a plasmid, pCArG-U2, was constructed by incorporating nine CArG elements (in tandem) of EGR1 gene upstream to uPA and uPAR siRNA oligonucleotides in a pCi-neo vector. Radiation-induced siRNA expression was detected in a meningioma cell line (IOMM-Lee). Immunoblotting and RT-PCR analyses confirmed downregulation of uPA and uPAR. A similar effect was observed in transfected cells followed by H2O2 treatment. Moreover, pre-treatment of transfected cells with N-acetyl L-cysteine blocked the silencing of uPA and uPAR, which further confirmed the oxidative damage-mediated downregulation. Cell proliferation assays and Western blot analysis for apoptotic molecules confirmed cell death in a radiation-inducible fashion. Migration and matrigel invasion assays also revealed a marked decrease in migration and invasion. Immunocytochemistry showed a marked decrease in uPA and uPAR levels in transfected and irradiated cells. H&E staining revealed a decrease in the pre-established tumor volume among the animals treated with pCArG-U2 and radiation. Immunohistochemistry of the brain sections established with intracranial tumors also revealed a marked decrease in uPA and uPAR in a radiation-inducible fashion. Taken together, our data suggest pCArG-U2 as a suitable candidate for radiation-inducible gene therapy.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20198323-10389872,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20198323-10757025,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20198323-10918478,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20198323-12163460,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20198323-12365005,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20198323-12424068,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20198323-19137013,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20198323-19301652,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20198323-2440339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20198323-8044769,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20198323-8664375
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1791-2423
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
36
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
809-16
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:20198323-Animals,
pubmed-meshheading:20198323-Apoptosis,
pubmed-meshheading:20198323-Blotting, Western,
pubmed-meshheading:20198323-Cell Line, Tumor,
pubmed-meshheading:20198323-Cell Movement,
pubmed-meshheading:20198323-Cell Proliferation,
pubmed-meshheading:20198323-Cell Survival,
pubmed-meshheading:20198323-Early Growth Response Protein 1,
pubmed-meshheading:20198323-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:20198323-Gene Therapy,
pubmed-meshheading:20198323-Humans,
pubmed-meshheading:20198323-Immunohistochemistry,
pubmed-meshheading:20198323-Meningeal Neoplasms,
pubmed-meshheading:20198323-Meningioma,
pubmed-meshheading:20198323-Mice,
pubmed-meshheading:20198323-Mice, Nude,
pubmed-meshheading:20198323-Neoplasm Invasiveness,
pubmed-meshheading:20198323-Oxidative Stress,
pubmed-meshheading:20198323-Promoter Regions, Genetic,
pubmed-meshheading:20198323-RNA, Small Interfering,
pubmed-meshheading:20198323-RNA Interference,
pubmed-meshheading:20198323-Radiotherapy, Adjuvant,
pubmed-meshheading:20198323-Receptors, Urokinase Plasminogen Activator,
pubmed-meshheading:20198323-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20198323-Time Factors,
pubmed-meshheading:20198323-Transfection,
pubmed-meshheading:20198323-Tumor Burden,
pubmed-meshheading:20198323-Urokinase-Type Plasminogen Activator,
pubmed-meshheading:20198323-Xenograft Model Antitumor Assays
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pubmed:year |
2010
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pubmed:articleTitle |
Radiation-inducible silencing of uPA and uPAR in vitro and in vivo in meningioma.
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pubmed:affiliation |
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA.
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