关键词: 雌激素, GPER, 乳腺癌, 乳腺癌耐药蛋白, 多药耐药性

Abstract: Objective To explore the interaction between ER and GPER in the process of estradiol-mediated regulation of ABCG2 in MCF-7 cells. Methods Western blot and immunoflurescent were used to detect the expression and localization of ABCG2 treated with 17-β estradiol( E2 ), G1 respectively or combined with inhibitors. The intervented cells mentioned above was treated doxorubicin (Dox), then the change of drug sensitivity was test by flow cytometry analysis and CCK8 method. Results ABCG2 localizes at both of plasma membrane and cytoplasm. E2 upregulates the level of ABCG2 protein and translocates it from cytoplasm to plasma membrane, which result in inhibiting the effect of chemotherapy drugs Dox . The relative protein expression of ABCG2 in E2 treatment group was higher than those of the control group( P<0.05) . Above-mentioned changes were blocked by E2 antagonist (TAM) ( P<0.05). The expression of ABCG2 was both downregulated in TAM and GPER specific angonist (G1) treatment groups( P<0.05). Cytotoxic of Dox was improved in those groups as well( P<0.05). The relative protein expression of ABCG2 were lower, which were blocked by GPER specific antagonist (G15). Conclusion Estradiol upregulates the expression of ABCG2 and weakens the effect of chemotherapy drugs in the case of activate ER and GPER simultaneously. On the contrary, acivating GPER specifically have an opposite result which improves the efficacy of chemotherapy.

Key words: estrogen, GPER, breast cancer, breast cancer resistance protein, MDR