Jing Xuanxuan, Zhang Hui, Hu Jing, Su Peng, Zhang Wei, Jia Ming, Cheng Hongxia, Li Weiwei, Zhou Gengyin
Department of Pathology, Shandong University School of Medicine 44 Wenhua Xi Road, Jinan 250012, Shandong, P. R. China.
Department of Pathology, Qilu Hospital of Shandong University 107 Wenhua Xi Road, Jinan 250012, Shandong, P.R. China.
Int J Clin Exp Pathol. 2015 Feb 1;8(2):1354-63. eCollection 2015.
Mutidrug resistance (MDR) severely blocks the successful management of breast cancer. Overexpression of MDR1/p-gp accounts for the major factor in the development of MDR. β-arrestin 2 has been reported to widely involve in multiple aspects of tumor development. In order to verify whether β-arrestin 2 regulates mutidrug resistance in breast cancer, we analyzed the protein expression levels of β-arrestin 2 and MDR1/p-gp by immunohistochemistry in 106 paraffin-embedded human breast tissue samples. There was a positive correlation between β-arrestin 2 and MDR1/p-gp protein expression (P = 0.016). Changes in MDR1/p-gp mRNA and protein levels were examined by quantitative real-time reverse polymerase chain reaction (qRT-PCR) and western blotting. Silencing of β-arrestin 2 evidently down-regulated the expression of MDR1/p-gp in transfected ADM cells. In contrast, overexpression of β-arrestin 2 had the opposite changes in MDA-MB-231 and MCF-7 cells. MTS assay revealed that silencing of β-arrestin 2 increased the sensitivity to anti-cancer drugs to some extent. On the other hand, overexpression of β-arrestin 2 had the opposite effects. Our above data demonstrate that β-arrestin 2 plays a vital role in the regulation of MDR1/p-gp expression in Breast cancer.
多药耐药（MDR）严重阻碍了乳腺癌的成功治疗。MDR1/p -糖蛋白的过表达是MDR发生的主要因素。据报道，β -抑制蛋白2广泛参与肿瘤发生发展的多个方面。为了验证β -抑制蛋白2是否调节乳腺癌的多药耐药，我们通过免疫组织化学分析了106例石蜡包埋的人乳腺组织样本中β -抑制蛋白2和MDR1/p -糖蛋白的蛋白表达水平。β -抑制蛋白2与MDR1/p -糖蛋白的蛋白表达呈正相关（P = 0.016）。通过定量实时逆转录聚合酶链反应（qRT - PCR）和蛋白质印迹法检测MDR1/p -糖蛋白mRNA和蛋白水平的变化。在转染的ADM细胞中，β -抑制蛋白2的沉默明显下调了MDR1/p -糖蛋白的表达。相反，在MDA - MB - 231和MCF - 7细胞中，β -抑制蛋白2的过表达则产生相反的变化。MTS检测显示，β -抑制蛋白2的沉默在一定程度上增加了对抗癌药物的敏感性。另一方面，β -抑制蛋白2的过表达则产生相反的效果。我们上述数据表明，β -抑制蛋白2在调节乳腺癌中MDR1/p -糖蛋白表达方面起着至关重要的作用。
