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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2003-4-17
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pubmed:abstractText |
Interferon-gamma (IFN-gamma) induced cell death in five oral squamous cell carcinoma (SCC) lines. Cell death was specific to IFN-gamma treatment and did not occur with either IFN-alpha or TNF-alpha. IFN-gamma did not induce typical apoptotic phenotype in cells, such as morphological changes and DNA ladder formation. Caspase-3 was partially activated by IFN-gamma. Protein levels of molecular chaperones were examined in cells treated with IFN-gamma. Among these, levels of heat shock protein 27 (Hsp27) were specifically reduced upon IFN-gamma treatment of oral SCC cells. Recombinant clones overexpressing Hsp27 were more resistant to IFN-gamma-induced cell death than parent cells. Conversely, cells expressing a dominant-negative mutant of Hsp27, in which three serine residues (15, 78 and 82) were replaced by glycine, were hypersensitive to the effects of IFN-gamma and exhibited a typical apoptotic phenotype. Pretreatment of cells with IFN-gamma enhanced apoptotic cell death induced by cisplatin. Our data suggest that IFN-gamma suppresses Hsp27 expression in oral SCC cells and blocks the inhibitory effects of this molecular chaperone on apoptotic cell death. Moreover, IFN-gamma initiates the transition of oral SCC cells to the proapoptotic and/or aborted apoptotic state. Hsp27 plays a crucial role in the inhibition of apoptosis of oral SCC cells. Our findings highlight the importance of employing IFN-gamma in combination with certain anticancer drugs as treatments for oral cancer. We suggest that Hsp27 plays a significant role in the IFN-gamma-induced sensitization of oral SCC cells to anticancer drugs.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/HSP27 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HSPB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Molecular Chaperones,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1350-9047
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
313-22
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12700631-Antineoplastic Agents,
pubmed-meshheading:12700631-Apoptosis,
pubmed-meshheading:12700631-Blotting, Western,
pubmed-meshheading:12700631-Carcinoma, Squamous Cell,
pubmed-meshheading:12700631-Caspase 3,
pubmed-meshheading:12700631-Caspases,
pubmed-meshheading:12700631-Cell Line, Tumor,
pubmed-meshheading:12700631-Cell Survival,
pubmed-meshheading:12700631-Chromatography, Gel,
pubmed-meshheading:12700631-Cisplatin,
pubmed-meshheading:12700631-Cytokines,
pubmed-meshheading:12700631-Dose-Response Relationship, Drug,
pubmed-meshheading:12700631-Down-Regulation,
pubmed-meshheading:12700631-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:12700631-Genes, Dominant,
pubmed-meshheading:12700631-HSP27 Heat-Shock Proteins,
pubmed-meshheading:12700631-Heat-Shock Proteins,
pubmed-meshheading:12700631-Humans,
pubmed-meshheading:12700631-Interferon-gamma,
pubmed-meshheading:12700631-Microscopy, Electron,
pubmed-meshheading:12700631-Molecular Chaperones,
pubmed-meshheading:12700631-Mouth Neoplasms,
pubmed-meshheading:12700631-Mutation,
pubmed-meshheading:12700631-Neoplasm Proteins,
pubmed-meshheading:12700631-Phenotype,
pubmed-meshheading:12700631-Plasmids,
pubmed-meshheading:12700631-Time Factors
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pubmed:year |
2003
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pubmed:articleTitle |
Interferon-gamma downregulates Hsp27 expression and suppresses the negative regulation of cell death in oral squamous cell carcinoma lines.
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pubmed:affiliation |
Department of Oral Surgery, Sapporo Medical University School of Medicine, Japan.
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pubmed:publicationType |
Journal Article
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