PRMT2 Combined With Tamoxifen CAN Increase The Cell Death And Its Mechanism In Breast Cancer Cells

Objective: To investigate the effect of Protein arginineme transferase 2(PRMT2)expression on cell death in breast cancer cells,and to provide new ideas for endocrine therapy in breast cancer patients.Methods: In order to investigate the role of PRMT2 in TAM induced apoptosis in breast cancer cells and its related mechanism,We carefully designed the experimental,mainly including four parts,Firstly,flow cytometry was used to explore the effect of different expression of PRMT2 on the cell death in breast cancer cells.Secondly,cell cycle assays were used to know the influence of overexpressed PRMT2 on breast cancer cells cycle.Thirdly,western blot was used to analyze the effect of PRMT2 on the ER-α36,Akt,and P-Akt expression.Fourthly,using immunohistochemical assays to determine PRMT2 and ER-α36 gene expression in breast cancer cells and its correlation.Results: 1.Flow cytometry results showed that MCF-7-sh PRMT2 cells,which treated with tamoxifen at 0μmol/L and 7.5μmol/L for 36 hours,showed significantly lower mortality rate(P<0.0001)than MCF-7-NC cells(P<0.0001).On the contrary,After treatment with tamoxifen at the same concentration,the mortality rate of MDA-MB-231-PRMT2 cells was significantly higher than MDA-MB-231-NC cells.(P<0.05)2.Cell cycle assay results suggested that compared with the control group of MDA-MB-231-NC cells,which treated with 0μmol/L and 5μmol/L tamoxifen for 36 hours,MDA-MB-231-PRMT2 cells showed significantly increased G1 phase arrest and significantly decreased S phase(reflected cell proliferation status).3.We established a tetracycline-induced lentivirus system to obtain stable MDA-MB-231-PRMT2 cells,WB results showed that compared with MDA-MB-231-NC cells in the control group,the expressions of ER-α36 and P-Akt in MDA-MB-231-PRMT2 cells were significantly reduced.On the contrary,We knock-down PRMT2 with the lentiviral sh RNA-based plasmid,Pyr-Lvsh-PRMT2,to obtain MCF-7-sh PRMT2 cells.Results showed that compared with MCF-7-NC cells in the control group,the expression of ER-α36 and P-Akt in MCF-7-sh PRMT2 cells was significantly increased.4.Histopathological sections were performed on 160 patients of breast cancer.Statistical analysis of breast cancer patients showed no significant correlation between ER-α36 and PRMT2.Conclusion:1.The overexpressed of PRMT2 combined with TAM can increase the mortality of MDA-MB-231 cells.2.In MDA-MB-231 cells and MCF-7 cells,the overexpressed of PRMT2 combined with TAM can increase cell death,and its mechanism may be related to the fact that PRMT2 can inhibit the expression of ER-α36 and its downstream PI3K/Akt pathway.