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Downregulation of the c-Fes protein-tyrosine kinase inhibits the proliferation of human renal carcinoma cells
http://hdl.handle.net/10069/22900
http://hdl.handle.net/10069/22900d66eba3b-b704-4ec1-97b0-19bf27b09b9f
名前 / ファイル | ライセンス | アクション |
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IJO34_89.pdf (444.6 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2010-02-08 | |||||
タイトル | ||||||
タイトル | Downregulation of the c-Fes protein-tyrosine kinase inhibits the proliferation of human renal carcinoma cells | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | human renal carcinoma cells | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | c-Fes | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | siRNA | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | proliferation | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Akt1 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | NFκB | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Kanda, Shigeru
× Kanda, Shigeru× Miyata, Yasuyoshi× Kanetake, Hiroshi× Smithgall, Thomas E. |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The c-Fes protein-tyrosine kinase is associated with growth and differentiation of hematopoietic, neuronal, vascular endothelial and epithelial cell types. In this study, we investigated whether small interfering RNA (siRNA)-mediated knockdown of c-Fes expression affected proliferation of the human renal carcinoma cell lines, ACHN and VMRC-RCW. Immunofluorescence microscopy showed that c-Fes was expressed in both the cytosol and nuclei of these cells, and siRNA treatment preferentially downregulated c-Fes expression in the cytosol. Knock-down of c-Fes inhibited cellular proliferation in a dose-dependent manner with minimal increase in cell death. c-Fes siRNA treatment also downregulated the phosphorylation of Akt1 on S473 and IKKα on T23, and cyclin D1 expression, enhanced the expression of IκBα, and prevented the nuclear localization of NFκB. Treatment with an NFκB inhibitory peptide (SN50) also blocked the proliferation and nuclear localization of NFκB in these cells. The effect of SN50 treatment was not enhanced by c-Fes siRNA, suggesting that downregulation of c-Fes expression inhibited cell cycle progression through the Akt1/NFκB pathway. In contrast to siRNA-mediated knockdown, ectopic expression of either wild-type or kinase-inactive c-Fes in renal carcinoma cells failed to alter their proliferation in vitro and in vivo. Thus, suppression of proliferation resulting from siRNA-mediated knockdown may depend upon an expression of c-Fes protein rather than its kinase activity. Taken together, our results indicate that downregulation of c-Fes expression may be a potential therapeutic strategy for advanced human renal cell carcinoma and inhibition of its kinase activity as an antiangiogenic therapy does not seem to induce the growth of human renal carcinoma cells. | |||||
書誌情報 |
International Journal of Oncology 巻 34, 号 1, p. 89-96, 発行日 2009-01 |
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出版者 | ||||||
出版者 | Spandidos Publications | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 10196439 | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1791-2423 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA10992511 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.3892/ijo_00000132 | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | International Journal of Oncology, 34(1), pp.89-96; 2009 |