Interferon-γ downregulates Hsp27 expression and suppresses the negative regulation of cell death in oral squamous cell carcinoma lines
| Autor: | Shin-ichi Yokota, Noriyuki Yonekura, Nobuhiro Fujii, Gen-iku Kohama, K Yonekura, Hironari Dehari, Satoru Arata |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
endocrine system
Programmed cell death Time Factors animal structures Cell Survival Blotting Western HSP27 Heat-Shock Proteins Down-Regulation Antineoplastic Agents Apoptosis Biology urologic and male genital diseases Interferon-gamma Hsp27 Interferon Cell Line Tumor medicine Humans Interferon gamma Molecular Biology Heat-Shock Proteins Genes Dominant Dose-Response Relationship Drug Caspase 3 Cell growth Neurodegeneration Cancer Cell Biology medicine.disease Neoplasm Proteins Gene Expression Regulation Neoplastic Microscopy Electron stomatognathic diseases Phenotype Caspases Mutation embryonic structures Carcinoma Squamous Cell Chromatography Gel Cancer research biology.protein Cytokines Mouth Neoplasms Cisplatin Molecular Chaperones Plasmids medicine.drug |
| Zdroj: | Cell Death & Differentiation. 10:313-322 |
| ISSN: | 1476-5403 1350-9047 |
| DOI: | 10.1038/sj.cdd.4401169 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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