EDN1 and nonpapillary renal cell carcinoma: However, we have previously demonstrated that, in addition to HIF-2α, VEGF protein levels are sensitive to mitogen-activated protein kinase signaling.27 Both extracellular regulated kinase 1/2 phosphorylation and VEGF are increased upon CPT treatment in RCC4 cells.27 In addition, PAI-1 is also regulated by p53.28 We were interested in exploring the CPT-mediated regulation of ET-1 levels further as little is known about the regulation of ET-1 in ccRCC.