Yuzhu Zhang
Longhua Hospital Affiliated to Shanghai University of TCM, China
Title: ETS1 is associated with cisplatinum resistance though IKKα/NF-βB pathway in MDAMB-231
Biography
Biography: Yuzhu Zhang
Abstract
MDA-MB-231/DDP had higher IC50 value of DDP, lower intracellular DDP concentration, lower apoptosis ratio than MDA-MB-231 cell line treated with DDP. Considering the intracellular DDP concentration difference, we tested drug-resistant membrane proteins (MRP2, P-gp and BCRP), which were remarkably increased in MDA-MB-231/DDP cells. Next, we found these increased membrane proteins were induced by the activation of NF-κB pathway in MDA-MB-231/DDP cells. Furthermore, ETS1, RPL6, RBBP8, BIRC2, PIK3A and RARS were six important genes for DDP-resistance based on PPI network and expression validation. However, it has been reported enforced over-expression of ETS1 induced IKKα mRNA and protein expression as well as IKKα promoter activity. Our results suggested the protein expression of ETS1 and IKKα were significantly up-regulated in MDA-MB-231/DDP cells. In addition, inhibition of ETS1 expression enhances chemo-sensitivity to DDP and reversed the activation of NF-κB pathway in MDA-MB-231/DDP cells, whether ETS-1 binds to the core IKKα promoter and strongly induces its activity. Now, our team is researching the corresponding sites between ETS1 and IKKαby dual-luciferase and chromatin immunoprecipitation technique (ChIP).
