88P Epo-Independent Functional Epo Receptor in Breast Cancer Enhances Estrogen Receptor Activity and Promotes Cell Proliferation

Abstract

ABSTRACT The main function of erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis, and recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. Recent clinical trials have indicated that rhEPO treatment can have a negative effect on tumor progression and patient survival. In addition, EPOR expression has been detected in different cancer forms. Today the presence and function of EPOR in different cancer forms are still controversial, in part because the specificity of existing anti-EPOR antibodies has been questioned. Here we report an in-house polyclonal antibody that reliably detects the full-length isoform of the EPOR and we show that breast cancer cell lines as well as breast cancer tissue express the receptor protein. However, rhEPO stimulation of EPOR expressing breast cancer cells did not result in increased proliferation or activation of EPOR (receptor phosphorylation) or phosphorylation of JAK2/STAT5/AKT/ERK, mediators of the classical EPOR signaling pathway. A function of the receptor was however demonstrated in EPOR knockdown experiments resulting in decreased proliferation in estrogen receptor positive (ER+) cancer cells, while these effects were not seen in ER- cells. EPOR knockdown decreased ER activity in ER+ breast cancer cells, which could explain the EPOR effect on proliferation. Also, EPOR knockdown improved tamoxifen effects in ER+ breast cancer cells. This is in accordance with our previous clinical observation that high EPOR expression in tumors correlates to impaired tamoxifen response in patients with ER+ breast cancer (Clin Cancer Res 2009;15(17);5552-9). In conclusion we show that EPOR protein is expressed in breast cancer cells where it appears to act as a novel EPO-independent proliferation factor in ER expressing breast cancer cells, possibly via its capacity to modulate ER activity. Disclosure All authors have declared no conflicts of interest.