Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Acta Biochim Biophys Sin (Shanghai). 2012 Sep;44(9):752-8. doi: 10.1093/abbs/gms058. Epub 2012 Jul 20.
Over-expression of MDR1 confers multidrug resistance (MDR) in cancers and remains a major cause for the failure of chemotherapy. In the present study, we found that V-Ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) could activate MDR1 transcription and P-glycoprotein (P-gp) expression in SGC7901 cells. Knockdown of ETS2 attenuated MDR1 transcription and P-gp expression, and increased the sensitivity of MDR cancer cells to cytotoxic drugs that were transported by P-gp in SGC7901/VCR cells. ETS2 could bind to the ETS2 sites on the MDR1 promoter and activate its transcription. The regulation of MDR1 expression by ETS2 may provide potential ways to overcome MDR in cancer treatment.
MDR1 的过度表达赋予癌症多药耐药性(MDR),仍然是化疗失败的主要原因。在本研究中,我们发现 ETS 结构域转录因子 2(ETS2)可激活 SGC7901 细胞中 MDR1 转录和 P-糖蛋白(P-gp)的表达。ETS2 的敲低可减弱 MDR1 转录和 P-gp 的表达,并增加 SGC7901/VCR 细胞中由 P-gp 转运的细胞毒药物对多药耐药癌细胞的敏感性。ETS2 可以与 MDR1 启动子上的 ETS2 结合位点结合并激活其转录。ETS2 对 MDR1 表达的调控可能为克服癌症治疗中的多药耐药性提供了潜在途径。