Abstract: ObjectiveTo investigate the proliferative effect of Cadmium on thyroid cancer cell WRO and the involvement of GPER1 in this process.Methods Expression of GPER1 in MCF-7, MDA-MB-231 and WRO cell lineswere detected by Western blot; Three cell lines were divided into 7 groups, respectively: control, Cd (250, 500, 750 and 1000 nmol/L), E2 (10 nmol/L) and G1 (10 nmol/L) groups, Cell proliferationwere measured by MTT method; WRO cell were divided into groups: 1) control, Cd (5, 10, 15 and 30 min), E2 (15 min) and G1 (15 min) groups; 2) control, G15, Cd+G15, E2 and E2+G15 groups; 3) control, Cd, Cd+scramble siRNA and Cd+GPER1 siRNA groups; expression of p-ERK, t-ERK, p-AKT or AKT were detected by Western blot under the above three situations; WRO cell were divided into 6 groups: control, Cd, Cd+G15, Cd+PD98095, Cd+LY294002and Cd+GPER1 siRNA groups, cell proliferation was measured by MTT method. Results Thyroid cancer cell WRO expresses GPER1. Cd promoted cell proliferation in low concentrations (P<0.05), 500nmol/L Cd exhibit the most effective proliferative effect. Cd induced rapid phosphorylation of ERK and AKT with time (P<0.05), which peaked at 15min. Cd-induced ERK and AKT phosphorylationwas inhibited (P<0.05) either by inhibitor for GPER1 or siRNA target GPER1.Cd-induced cell proliferationwas suppressed (P<0.05) byG15，LY294002，PD98059 and GPER1 siRNA. ConclusionsGPER1-ERK/AKT signaling pathway was involved in Cd-induced proliferation of GPER1-positive thyroid cancer cell WRO.

Key words: Cadmium, GPER1, thyroid cancer, proliferation