Involvement of V-Ets erythroblastosis virus E26 oncogene homolog 2 in regulation of transcription activity of <italic>MDR1</italic> gene

Abstract

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.

Teaching an old dog new tricks: reactivated developmental signaling pathways regulate ABCB1 and chemoresistance in cancer

“…In paclitaxel-resistant prostate cancer PC3 cells, ETS1 silencing inhibited the activity of the ABCB1 promoter, which contains ETS binding sites, reduced ABCB1 protein, and reversed resistance to paclitaxel [ 260 ] , an antimicrotubule drug. ETS mediated regulation of ABCB1 was verified in a gastric cancer cell line exhibiting enhanced ABCB1 expression and vincristine resistance using ETS2 overexpression combined with ChIP assays [ 261 ] . At the level of FGF, immunohistochemical studies of bladder cancer tissue from patients showed correlation between basic FGF and ABCB1 signals [ 262 ] .…”