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Downregulation of the c-Fes protein-tyrosine kinase inhibits the proliferation of human renal carcinoma cells


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タイトル: Downregulation of the c-Fes protein-tyrosine kinase inhibits the proliferation of human renal carcinoma cells
著者: Kanda, Shigeru / Miyata, Yasuyoshi / Kanetake, Hiroshi / Smithgall, Thomas E.
発行日: 2009年 1月
出版者: Spandidos Publications
引用: International Journal of Oncology, 34(1), pp.89-96; 2009
抄録: 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.
キーワード: human renal carcinoma cells / c-Fes / siRNA / proliferation / Akt1 / NFκB
URI: http://hdl.handle.net/10069/22900
ISSN: 10196439
DOI: 10.3892/ijo_00000132
資料タイプ: Journal Article
原稿種類: publisher
出現コレクション:110 学術雑誌論文

引用URI : http://hdl.handle.net/10069/22900

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