Hypoxia stimulates the expression of HIF-1α and GPER through ERK1/2 activation in CAFs. The treatment with 100 μM CoCl2 (a) or the exposure to low oxygen tension (2% O2 for 30 minutes) (b) induce ERK1/2 phosphorylation, which is prevented by using 300 μM of the free radical scavenger NAC (c). (d) Immunoblots of HIF-1α and GPER from CAFs treated for 3 h with vehicle (-) or 100 μM CoCl2 alone and in combination with 300 μM NAC or 10 μM ERK1/2 inhibitor PD. Results shown are representative of three independent experiments. Side panels show densitometric analysis of the blots normalized to ERK/2 or β-actin. (○), (●) P < 0.05 for cells receiving vehicle (-) or cultured under normoxia vs cells treated with CoCl2 or cells cultured under hypoxia.