Jeong Yisun, You Daeun, Kang Hyun-Gu, Yu Jonghan, Kim Seok Won, Nam Seok Jin, Lee Jeong Eon, Kim Sangmin
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea.
Breast Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
J Breast Cancer. 2018 Mar;21(1):21-27. doi: 10.4048/jbc.2018.21.1.21. Epub 2018 Mar 23.
The exact mechanism regulating fibronectin (FN) expression in breast cancer cells has not been fully elucidated. In this study, we investigated the pharmacological mechanism of berberine (BBR) with respect to FN expression in triple-negative breast cancer (TNBC) cells.
The clinical significance of FN mRNA expression was analyzed using the Kaplan-Meier plotter database (http://kmplot.com/breast). FN mRNA and protein expression levels were analyzed by real-time polymerase chain reaction and western blotting, respectively.
Using publicly available clinical data, we observed that high FN expression was associated with poor prognosis in patients with breast cancer. FN mRNA and protein expression was increased in TNBC cells compared with non-TNBC cells. As expected, recombinant human FN significantly induced cell spreading and adhesion in MDA-MB231 TNBC cells. We also investigated the regulatory mechanism underlying FN expression. Basal levels of FN mRNA and protein expression were downregulated by a specific activator protein-1 (AP-1) inhibitor, SR11302. Interestingly, FN expression in TNBC cells was dose-dependently decreased by BBR treatment. The level of c-Jun phosphorylation was also decreased by BBR treatment.
Our findings demonstrate that FN expression is regulated via an AP-1-dependent mechanism, and that BBR suppresses FN expression in TNBC cells through inhibition of AP-1 activity.
乳腺癌细胞中调节纤连蛋白（FN）表达的确切机制尚未完全阐明。在本研究中，我们研究了黄连素（BBR）对三阴性乳腺癌（TNBC）细胞中FN表达的药理机制。
使用Kaplan-Meier绘图仪数据库（http://kmplot.com/breast）分析FN mRNA表达的临床意义。分别通过实时聚合酶链反应和蛋白质印迹法分析FN mRNA和蛋白质表达水平。
利用公开的临床数据，我们观察到FN高表达与乳腺癌患者的不良预后相关。与非TNBC细胞相比，TNBC细胞中FN mRNA和蛋白质表达增加。正如预期的那样，重组人FN显著诱导MDA-MB231 TNBC细胞的细胞铺展和黏附。我们还研究了FN表达的调控机制。特异性激活蛋白-1（AP-1）抑制剂SR11302下调了FN mRNA和蛋白质表达的基础水平。有趣的是，BBR处理以剂量依赖性方式降低了TNBC细胞中的FN表达。BBR处理也降低了c-Jun磷酸化水平。
我们的研究结果表明，FN表达通过AP-1依赖性机制调节，并且BBR通过抑制AP-1活性抑制TNBC细胞中的FN表达。
