Objective The aim of this study was to investigate the regulatory role and mechanism of TRIM24 in endocrine therapy resistance of breast cancer.Methods The relationship between TRIM24 expression and prognosis in breast cancer patients receiving endocrine therapy was analyzed by the Kaplan-Meier Plotter database.After treatment of breast cancer MCF7 cells or T47D cells with tamoxifen(TAM),the expression of TRIM24 was detected by qRT-PCR and Western blot.After knocking out TRIM24 in TAM sensitive MCF7/S0.5 cells and resistant cells MCF7/TAMR-1 cells,cell proliferation was measured by CCK 8 assay.After knocking out the estrogen receptor(ER)or treating with the selective progesterone receptor(PR)antagonist UPA(Ulipristal acetate)in MCF7 cells,the expression of TRIM24 was measured by qRT-PCR and Western blot.After PR was overexpressed in MCF7 cells,the expression of TRIM24 was detected by Western blot.The expression of human epidermal growth factor receptor 2(HER2)was detected by qRT PCR and Western blot after the overexpression of TRIM24.Results Among breast cancer patients receiving endocrine thera-py,patients with high expression of TRIM24 had a shorter recurrence free survival(RFS)(P=0.027).TAM treatment could induce an increase of TRIM24 expression(P<0.001);Knocking out TRIM24 significantly inhibited the proliferation of drug-resistant MCF7/TAMR-1 cells(P<0.001),but had no effect on sensitive MCF7/S0.5 cells;After knocking out ER or treatment of PR antagonist,the expression of TRIM24 could be upregulated in MCF7 cells(P<0.01),while overexpression of PR could down-regulate the expression of TRIM24.TRIM24 could activate the expression of HER2(P<0.05).Conclusion PR negatively regulation of TRIM24 plays an important role in endocrine therapy resistance of breast cancer.

Objective The aim of this study was to investigate the regulatory role and mechanism of TRIM24 in endocrine therapy resistance of breast cancer.Methods The relationship between TRIM24 expression and prognosis in breast cancer patients receiving endocrine therapy was analyzed by the Kaplan-Meier Plotter database.After treatment of breast cancer MCF7 cells or T47D cells with tamoxifen(TAM),the expression of TRIM24 was detected by qRT-PCR and Western blot.After knocking out TRIM24 in TAM sensitive MCF7/S0.5 cells and resistant cells MCF7/TAMR-1 cells,cell proliferation was measured by CCK 8 assay.After knocking out the estrogen receptor(ER)or treating with the selective progesterone receptor(PR)antagonist UPA(Ulipristal acetate)in MCF7 cells,the expression of TRIM24 was measured by qRT-PCR and Western blot.After PR was overexpressed in MCF7 cells,the expression of TRIM24 was detected by Western blot.The expression of human epidermal growth factor receptor 2(HER2)was detected by qRT PCR and Western blot after the overexpression of TRIM24.Results Among breast cancer patients receiving endocrine thera-py,patients with high expression of TRIM24 had a shorter recurrence free survival(RFS)(P=0.027).TAM treatment could induce an increase of TRIM24 expression(P<0.001);Knocking out TRIM24 significantly inhibited the proliferation of drug-resistant MCF7/TAMR-1 cells(P<0.001),but had no effect on sensitive MCF7/S0.5 cells;After knocking out ER or treatment of PR antagonist,the expression of TRIM24 could be upregulated in MCF7 cells(P<0.01),while overexpression of PR could down-regulate the expression of TRIM24.TRIM24 could activate the expression of HER2(P<0.05).Conclusion PR negatively regulation of TRIM24 plays an important role in endocrine therapy resistance of breast cancer.