TRIM24在乳腺癌内分泌治疗耐药中的作用及机制研究  

The role and mechanism of TRIM24 in endocrine therapy resistance of breast cancer

作　　者：庞琬莹 安静 刘兆良 PANG Wanying;AN Jing;LIU Zhaoliang(Institute of Cancer Prevention and Treatment,Harbin Medical University,Harbin 150081,China)

机构地区：[1]哈尔滨医科大学肿瘤防治研究所,哈尔滨150081

出　　处：《实用肿瘤学杂志》2024年第6期402-409,共8页Practical Oncology Journal

基　　金：黑龙江省自然科学基金联合引导项目(编号:LH2021H058)。

摘　　要：目的探讨TRIM24在乳腺癌内分泌治疗耐药中的调控作用及作用机制。方法通过Kaplan-Meier Plotter数据库分析接受内分泌治疗的乳腺癌患者中TRIM24表达与预后的关系。使用他莫昔芬(Tamoxifen,TAM)处理乳腺癌细胞MCF7或T47D后,应用qRT-PCR及Western blot法检测TRIM24的表达。在TAM敏感细胞MCF7/S0.5和耐药细胞MCF7/TAMR-1中敲除TRIM24后,CCK-8法检测细胞增殖情况。在MCF7细胞中敲除雌激素受体(Estrogen receptor,ER)或使用选择性孕酮受体(Progesterone receptor,PR)拮抗剂醋酸乌利司他(Ulipristal acetate,UPA)处理后,通过qRT-PCR及Western blot法检测TRIM24的表达情况。在MCF7中过表达PR后,Western blot法检测TRIM24的表达变化。过表达TRIM24后通过qRT-PCR及Western blot法检测人表皮生长因子受体2(Human epidermal growth factor receptor 2,HER2)的表达。结果在接受内分泌治疗的乳腺癌患者中,TRIM24高表达患者的无复发生存期(Recurrence free survival,RFS)更短(P=0.027)。TAM处理能够诱导TRIM24表达升高(P<0.001)。敲除TRIM24可以显著抑制耐药细胞MCF7/TAMR-1的增殖(P<0.001),而对敏感细胞MCF7/S0.5没有影响。敲除ER或使用PR拮抗剂处理后能够上调TRIM24的表达(P<0.01),而过表达PR后能够下调TRIM24的表达。TRIM24可以激活HER2表达(P<0.05)。结论PR负调控TRIM24在乳腺癌内分泌治疗耐药中发挥重要作用。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.

关 键 词：TRIM24 他莫昔芬 孕激素受体 内分泌治疗耐药 

分 类 号：R737.9[医药卫生—肿瘤]