Erythropoietin receptor induces a paclitaxel resistance phenotype in mammary adenocarcinoma cells

Abstract

While erythropoietin (EPO) regulates erythropoiesis, the erythropoietin receptor (EPOR) has been identified in many non-hematopoietic cells, including cancer. Our previous study demonstrated that overexpression of EPOR altered the cell growth and the sensitivity of RAMA 37 breast cancer cells to tamoxifen. Indeed, results of the present study uncovered the role of EPOR in the resistance of EPOR-overexpressing RAMA 37-28 cells to paclitaxel chemotherapy. In this regard, EPOR silencing in the presence of paclitaxel therapy decreased RAMA 37-28 cell proliferation, confirming its role in the sensitivity or resistance of RAMA 37-28 cells to paclitaxel. Notably, compared to parental RAMA 37 cells, RAMA 37-28 cells also showed a lower rate of apoptosis induced by paclitaxel, as monitored by caspase 3/7 activation and Annexin V by IncuCyte ZOOM system. Moreover, enhanced activation of signaling pathways mediated by pERK1/2 in RAMA 37-28 cells as detected by western blot analysis was demonstrated to be essential for paclitaxel resistance.