VHL and renal cell carcinoma: In this RCC model the vast majority (122/160) of genes induced by hypoxia in wt-VHL transfected 786-O (VHL+) cells are not significantly up-regulated in VHL mutated 786-O cells, confirming that the loss of VHL is not equivalent to hypoxic exposure and that in RCC, the VHL tumor suppressor has a distinct role from its activity in the hypoxia-inducible pathway [57].