| Background:Breast cancer is common worldwide.EMT(Epithelial-mesenchymal transition)plays an important role in invasion and metastasis of breast cancer.Our previous study has indicated that overexpression of S100A16 promoted EMT via Notch 1 pathway in breast cancer.It is reported that EMT accelerated tamoxifen resistance by certain ways.However,the role of S100A16 in tamoxifen resistance of breast cancer cells remains to be clarified.The phenomenon of tamoxifen resistance is usual and the underlying mechanism is comprehensive,of which the loss or low expression of ERa and PI3K/AKT-mediated activation of ERα is of importance.Purpose:To explore the relationship between expression of S100A16 and the sensibility of breast cancer cells to tamoxifen.Materials and methods:In our study,the role of the upregulation of S100A16 in the sensibility of MCF-7 cells to tamoxifen was determined by cytotoxicity assays and colony formation assays,and the influence of overexpression of S100A16 on apoptosis and necrosis of MCF-7 cells induced by tamoxifen was investigated via flow cytometry analysis.We explored the alteration of the pathway associated with ERa in MCF-7/S100A16 cells by western blot and qRT-PCR.PI3K inhibitor and mTOR inhibitor were used to demonstrated the importance of PI3K/AKT-mediated activation of ERa in resistance of tamoxifen.Result:Overexpression of S100A16 reduced the growth inhibition rate of tamoxifen to MCF-7 cells in cytotoxicity assays and colony formation assays.In flow cytometry analysis,we found that both apoptosis and necrosis of MCF-7 cells induced by tamoxifen decreased due to overexpression of S100A16.In our study,we found that overexpression of S100A16 facilitated the downregulation of ERa in mRNA level and protein level and upregulation of phosphorylated AKT(Ser473),phosphorylated mTOR(Ser2448),phosphorylated P70S6K(Thr389),phosphorylated ERa(Serl67)by western blotting.Moreover,PI3K inhibitor LY294002 and mTOR inhibitor Rapamycin could downregulate the expression of p-ERa(Serl67)and partly revesed the tamoxifen resistance caused by overexpression of S100A16 in cytotoxicity assays and flow cytometry assays,respectively.Conclusion:our study demonstrated that overexpression of S100A16 promoted the resistance of MCF-7 cells to tamoxifen via downregulation of ERα and the activation of ERa via PI3K/AKT pathway. |
