Objective      To explore the effects of estrogen on the proliferation of triple-negative breast cancer cell line MDA-MB-468 mediated by G protein-coupled estrogen receptor GPR30.        Methods      Fluorescence immunoassay and W

estern blotting were performed to examine the localization and expression of GPR30 in MDA-MB-468 cells. Cell cycle and cell proliferation were tested by flow cytometry and CCK-8 assay. The expression of phospho-extracellular regulate kinase (p-ERK) and Cyclin D1 was detected by Western blotting.        Results      GPR30 was detected with high expression level in the MDA-MB-468 cells and located mostly in the cytoplasm. After treatment with 17-β-estradiol (E

2

)

GPR30 specific agonist (G1) and tamoxifen (TAM)

the progression of cell cycle and cell proliferation was increased remarkably. The DNA contents in DNA synthesis (S) phase were 2.81±0.11

2.82±0.21

and 2.70±0.20 times higher and the relative cell numbers were 1.83±0.18

1.94±0.12

and 1.92±0.16 times higher than those of the control group

respectively. The above effects induced by E

2

G1 and TAM could be blocked by GPR30 specific antagonist G15 (

P

0.05). The relative protein level of p-ERK in the E

2

G1 and TAM treatment groups was 2.59±0.21

2.43±0.25

and 2.26±0.34 times higher and that of cyclin D1 was 1.67±0.06

1.51±0.08

1.90±0.07 times higher than those of the control group

respectively (

P

0.05). Interestingly

the changes induced by E

2

G1 and TAM were  inhibited by G15 (

P

0.05).       Conclusion      Estrogen triggers downstream ERK signaling by activating GPR30 to up-regulate the expression of p-ERK and cyclin D1

which accelerates MDA-MB-468 cell cycle progression

leading to abnormal cell proliferation.