VHL and renal cell carcinoma: Specifically, the activation of the HIF-1 mediated pathway that induces CA IX expression can be due to a reduction in cellular O2 levels, an activation of signaling pathways via the presents of growth factors and inflammatory response elements, and in some cases due to mutations in the tumor suppressor, VHL as seen in cases of renal cell carcinoma (RCC) where CA IX is homogenously expressed [27].