Abstract 3464: The effect of EPO-receptor in estrogen receptor positive breast cancer

Abstract

Abstract The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, recent clinical trials have indicated that rhEPO treatment might promote tumor progression and have a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα+) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity in ERα+ breast cancer cells and diminished ERα+ phosphorylation on Ser118, results that further support a mechanism by which EPOR affects proliferation via ERα+ mediated mechanisms. In conclusion, we show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation in ERα+ expressing breast cancer cells, in part via its capacity to positively modulate ERα activity. Citation Format: Marica C. Vaapil, Susann Reinbothe, Anna-Maria Larsson, Caroline Wigerup, Jianmin Sun, Annika Jögi, Drorit Neumann, Lars Rönnstrand, Sven Påhlman. The effect of EPO-receptor in estrogen receptor positive breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3464. doi:10.1158/1538-7445.AM2014-3464