Zhang Yuexing, Akinmade Damilola, Hamburger Anne W
Department of Pathology, University of Maryland, Baltimore, MD, United States.
Cancer Lett. 2008 Jul 8;265(2):298-306. doi: 10.1016/j.canlet.2008.02.024. Epub 2008 Mar 19.
The ErbB2/3 heterodimer plays a critical role in breast cancer genesis and progression. EBP1, an ErbB3 binding protein, inhibits breast cancer growth but its effects on ErbB3 ligand mediated signal transduction or ErbB receptors is not known. We report here that ectopic expression of EBP1 in MCF-7 and AU565 breast cancer cell lines inhibited HRG-induced proliferation. ErbB2 protein levels were substantially decreased in EBP1 transfectants, while ErbB3 levels were unchanged. HRG-induced AKT activation was attenuated in EBP1 stable transfectants and transfection of a constitutively activated AKT partially restored the growth response to HRG. Down-regulation of EBP1 expression in MCF-7 cells by shRNA resulted in increased cell growth in response to HRG and increased cyclin D1 and ErbB2 expression. These results suggest that EBP1, by down-regulating ErbB signal transduction, attentuates HRG-mediated growth of breast cancer cells.
ErbB2/3异二聚体在乳腺癌的发生和发展中起关键作用。EBP1是一种与ErbB3结合的蛋白,可抑制乳腺癌生长,但其对ErbB3配体介导的信号转导或ErbB受体的影响尚不清楚。我们在此报告,在MCF-7和AU565乳腺癌细胞系中异位表达EBP1可抑制HRG诱导的增殖。在EBP1转染细胞中,ErbB2蛋白水平显著降低,而ErbB3水平未改变。在EBP1稳定转染细胞中,HRG诱导的AKT激活减弱,转染组成型激活的AKT可部分恢复对HRG的生长反应。通过shRNA下调MCF-7细胞中EBP1的表达,可导致对HRG的细胞生长增加以及细胞周期蛋白D1和ErbB2表达增加。这些结果表明,EBP1通过下调ErbB信号转导,减弱了HRG介导的乳腺癌细胞生长。