Fig. 2.
HIF2α activation results in induction of EGFR protein levels. (A) Western blot analysis of EGFR, HIFα, and GLUT levels in U87MG cells infected with adenovirus expressing flag-tagged GFP or a dominant-negative form of HIF (dnHIF). Cells were grown as 3D spheroids for 3 days. Control cells were grown in 2D culture for the same period. (B) Western blot analysis of EGFR and HIFα levels in U87MG and MDA-MB-231 cells infected with GFP or dnHIF for 24 h. before exposure to normoxia or hypoxia for an additional 24 h. (C and D) Western blot (C) and RT-PCR (D) analysis of EGFR levels in U87MG cells infected to express GFP or HIFα variants (HIF1α and HIF2α) for 72 h in normoxia. (E) Western blot analysis of EGFR and HIFα levels in U87MG transiently transfected with siRNA (50 nM) targeting HIF1α (siHIF1α), HIF2α (siHIF2α), or a scramble sequence (siCont) for 48 h before exposure to hypoxia for an additional 24 h. (F) Western blot analysis of EGFR and HIF2α levels in U87MG pretreated with 10 nM rapamycin (Rap), or DMSO as a vehicle control, for 1 h and then exposed to normoxia or hypoxia for an additional 16 h. The phosphorylation status of the S6 ribosomal protein (ph-S6) served as a control for drug activity. Actin served as a loading control in A–F.