Objective      To explore the effect of estrogen on the proliferation of human breast cancer cell line SKBR-3 mediated by G protein-coupled estrogen receptor (GPER).       Methods      Calcium influx

cell growth ability and cell cycle were examined by confocal laser scanning microscopy

CCK-8 assay and flow cytometry in the presence of d

ifferent concentrations of drugs

respectively. The relative expression level of phospho-extracellular signal-regulated kinase (p-ERK) was detected by Western blotting.       Results      After the cells were treated with 17-β estradiol (E

2

) or GFER specific agonist (G1)

intracellular calcium ion concentration shifted quickly from 120 seconds

and cell proliferation increased significantly with the relative cell numbers (2.08±0.07) times and (2.0±0.04) times more than those of the control group. The proliferation index (PI) (43.12±0.38)% and (42.43±0.52)% at S phase and G2-M phase increased significantly as compared to the control group (29.19±0.29)% (P0.05). The protein level of p-ERK was higher in the treatment group than in the control group (P0.05). GFPE antagonist G15

EGFR antagonist AG1478 and ERK antagonist U0126 rather than PI3K antagonist wortmannin could inhibit the changes induced by E

2

or G1.       Conclusion      Estrogen activates GPER-EGFR-ERK pathway to promote the proliferation of human breast cancer cell line SKBR-3.