A Discussion On The Role Of GPER1in The Mechanisms Of Tamoxifen Resistance In Breast Cancer

Objective To elucidate the role of GPER1in the mechanisms ofresistance to tamoxifen(TAM) endocrine therapy in breast cancer, thehuman breast cancer MCF-7tamoxifen-resistance cells and xenograftswere established.Methods MCF-7TAM-resistant cell line was derived by clonalselection in high concentration of4-hydroxytamoxifen (4-OHT) for a shortperiod[1]. Drug tolerance of MCF-7TAM-resistant cells were characterizedby investigating cells morphology, cellular growth curve, drug toxicity tests,cell cycle and Western blot. After induced a stable MCF-7TAM-resistantsubline, drug response tests, Western blot, RT-PCR and FCM were used todetected the role of GPER1in development of TAM resistance in breastcancer. Meanwhile xenografts model was established, the role of GPER1inresistant xenografts was investigated by measuring tumor volume.Results MCF-7TAM-resistant subline, which was derived by clonalselection in high concentration of OHT for a short period[1], showedsignificant resistance to TAM. Compared to MCF-7parental cells, E2、G1 and4-OHT induced a stronger cell proliferation of MCF-7/TAM-R cells;the activity of Erk1/2was enhanced which could be reduced by inhibitingGPER1in MCF-7/TAM-R cells; the expression of GPER1in cell surfacewas increased, whereas its total expression was not changed; blockade ofGPER1was not only increased the apoptosis of drug resistant cells, butalso restored the response to TAM in drug resistant tumorsConclusion GPER1played an important role in development of TAMresitance in breast cancer.