Objective      To investigate the effect of G protein-coupled estrogen receptor (GPER) on pro-apoptotic protein Bim in tamoxifen (TAM)-resistant breast cancer cells MCF-7R and related mechanism.       Methods      Human breast cancer cells MCF-7 and the MCF-7R cells were treated with 1 μmol/L TAM

and the cell morphological change was observed with an inverted microscope. The Bim mRNA expression was detected by quantitative real-time PCR (qRT-PCR) in the MCF-7 cells and MCF-7R cells. The expression of Bim protein

total GPER

and GPER in the cell membrane was detected by Western blotting. After the two kinds of cells were treated with ethanol

TAM

TAM+G15 (GPER specific inhibitor)

and G1 (GPER specific agonist)

the Bim protein expression was analyzed by Western blotting. After inhibiting the PI3K/AKT and MAPK/Erk signaling pathways in the MCF-7R cells

TAM was added

and then the Bim protein expression was assayed. Flow cytometry was adopted to detect cell apoptosis.       Results      After treatment with TAM

most of MCF-7 cells became bright and were suspended

while the MCF-7R cells had no obvious changes. The levels of Bim mRNA and protein in the MCF-7R cells were obviously lower than those in the MCF-7 cells (P0.05). The total GPER had no significant difference between the 2 kinds of cells

but GPER in the cell membrane was increased in the MCF-7R cells (P0.05). The expression of Bim protein was increased in the MCF-7 cells treated with TAM (P0.05)

but not in the MCF-7R cells. However

Bim protein was increased in the MCF-7R cells treated with G15 and then TAM (P0.05). The PI3K/AKT and MAPK/Erk signaling pathways stayed in the activated stage in the MCF-7R cells. When TAM was added after inhibiting MAPK/Erk pathway rather than PI3K/AKT pathway

the Bim protein was significantly increased (P0.05).TAM could promote the apoptosis of the MCF-7 cells

but not the MCF-7R cells. However

the apoptosis of MCF-7R cells was increased after GPER or MAPK/Erk signaling pathway was inhibited and then TAM was added (P0.05).       Conclusion      TAM as GPER agonist can activate the MAPK/Erk signaling pathway and inhibit the Bim expression in the MCF-7R cells. The MCF-7R cells are sensitive to TAM again through inhibiting GPER or MAPK/Erk signaling pathway.