MRTF-A在体内和体外调控乳腺癌发展过程中COL1A1基因的表达  

MRTF-A mediates the expression of COL1A1 in progression of breast cancer in vivo and vitro

作　　者：王琳 曹晓焱 王少华 WANG Lin;CAO Xiao-yan;WANG Shao-hua(Department of Medical Imaging,Women&Children Health Institute Futian,Shenzhen Guangdong 518000,China;Department of Pediatrics,Women&Children Health Institute Futian,Shenzhen Guangdong 518000,China)

机构地区：[1]深圳市福田区妇幼保健院医学影像科,广东深圳518000 [2]深圳市福田区妇幼保健院医学儿科,广东深圳518000

出　　处：《临床和实验医学杂志》2018年第23期2487-2490,共4页Journal of Clinical and Experimental Medicine

基　　金：广东省科技计划项目(编号:2011B031800114)

摘　　要：目的探讨心肌素相关转录因子-A (MRTF-A)对乳腺癌中I型胶原蛋白基因(COL1A1)基因表达的调控机制。方法选取18例经彩色多普勒超声确定为乳腺肿块的患者,后经病理检查,8例为良性,10例为恶性。实时定量PCR检测乳腺肿块及人乳腺癌细胞中MRTF-A和COL1A1的表达。MRTF-A干扰RNA转染乳腺癌细胞后,检测COL1A1的表达,荧光素酶报告检测MRTF-A与COL1A1启动子的结合。染色质免疫共沉淀(Ch IP)检测MRTF-A对COL1A1转录的影响。Wnt 3a和-catenin干扰RNA转染乳腺癌细胞后,检测MRTF-A和COL1A1的表达。结果MRTF-A和COL1A1在恶性肿块的表达显著高于其在良性肿块的表达。MRTF-A沉默可以抑制COL1A1 mRNA的表达,且降低COL1A1启动子荧光素酶活性。MRTF-A可与COL1A1启动子上CAr G DNA片段有效结合,MRTF-A沉默可降低乙酰化组蛋白H3K9和RNA聚合酶Ⅱ在COL1A1启动子处富集。Wnt 3a及-catenin在恶性肿块中的表达显著高于其在良性肿块中的表达,且无论是Wnt 3a沉默还是-catenin沉默均可显著抑制MRTF-A和COL1A1的表达。结论MRTF-A通过激活COL1A1的转录促进乳腺癌转移,Wnt/-catenin信号可调控此过程。Objective To investigate the regulatory mechanism of MRTF-A on COL1A1 expression in breast cancer.Methods 18 patients with breast lumps diagnosed by color Doppler ultrasound were selected(8 benign and 10 malignant pathologically).MRTF-A and COL1A1 expression in lump/cancer cells was assayed by real-time quantitative PCR.The expression of COL1A1 was assayed after MRTF-A interfering RNA transfection.The binding of MRTF-A to the COL1A1 promoter was by luciferase reporter assay.Analysis of COL1A1 transcription affected by MRTF-A was through chromatin immunoprecipitation(ChIP).The expression of MRTF-A and COL1A1 was assayed after Wnt 3a and-catenin interfering RNA transfection.Results The expressions of MRTF-A and COL1A1 in breast cancer cells were significantly higher than in benign lumps.COL1A1 mRNA expression was significantly silenced by MRTF-A and luciferase activity in COL1A1 promoter decreased.The expressions of Wnt 3a and-catenin in breast cancer cells were significantly higher than in benign lumps,and both Wnt 3a and-catenin silencing significantly inhibited the expression of MRTF-A and COL1A1.Conclusion MRTF-A promotes breast cancer metastasis by activating COL1A1.Wnt/-catenin pathway regulates this process.

关 键 词：乳腺癌 心肌素相关转录因子-A I型胶原蛋白基因 

分 类 号：R737.9[医药卫生—肿瘤]