Therefore, in addition to the HIF1α-mediated intrinsic hypoxia prominent in both empty vector control and Hif2α-expressing MPC, HIF2α-mediated pseudohypoxia further enhances radioresistance in pheochromocytoma cells by protecting the more radiosensitive outer cell layers (Figure 4A). This evidence concerns the gene EPAS1 and hereditary pheochromocytoma-paraganglioma.