Interaction of molecules with VHL-signaling pathway in renal cell carcinoma

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In this study, we focused on Twist, which is involved in EMT (epithelial-mesenchymal transition) and demonstrated its effect on VHL-HIF signaling pathway.Transcriptional activity of VEGF by Twist was measured by reporter assay using HIF responsive element (HRE) reporter plasmids co-transfected with Twist expression plasmid. Overexpressed Twist activated HRE reporter activity. VEGF promoter activity was activated by Twist in hypoxia.Binding of Twist to VEGF promoter in tumor cells were shown by chromatin immunoprecipitation (ChIP) assay using antibody against Twist. ChIP assay showed Twist binding to VEGF promoter. Electrophoresis Mobility Shift Assay (EMSA) were demonstrated to show binding of Twist for specific sequence (about -1000bp upstream from start point of transcription) in VEGF promoter.These data suggest that Twist expression involves in tumor vascularization in renal tumor.