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. 2019 Mar 5;9:3480. doi: 10.1038/s41598-019-39843-6

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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FGFR2 inhibits HIF-1 by repressing the CAD activity. (a) DU145 and PC3 cells were co-transfected with EPO enhancer-Luc plasmid, CMV-β-gal plasmid, and si-FGFR2 (or FGFR2-FLAG), and incubated under normoxic or hypoxic conditions for 16 hours. Luciferase activities were determined and presented as relative values (the means + SD, n = 3) versus the normoxic control. * and ** denotes p < 0.05 and p < 0.01 between the indicated groups, respectively. (b,c) DU145 and PC3 cells, which had been transfected with si-FGFR2 or FGFR2-FLAG, were incubated under normoxic or hypoxic conditions for 24 hours and subjected to immunoblotting with the indicated antibodies. HIF-1α, and HIF-2α blots were quantified by densitometry measurements with ImageJ (right panel). (d,e) DU145 and PC3 cells were co-transfected with Gal4_promoter-Luc reporter, Gal4_DBD-HIF-1α_CAD (or CAD N803A), and si-FGFR2 (or FGFR2-FLAG). Cells were incubated in normoxia or hypoxia for 16 hours and lysed to measure luciferase activities. Each bar represents the mean + SD (n = 3). * and N.S. denote p < 0.05 and p > 0.05 between the indicated groups, respectively.