VHL and neoplasm: Loss of VHL function leads to the accumulation of HIF-1α and HIF-2α, which consequently facilitates transcription of the hypoxia response genes, such as genes in vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and transforming growth factor alpha (TGF-α), eventually, resulting in angiogenesis and progression of tumor (Kourembanas et al., 1990; de Paulsen et al., 2001).