the erythropoietinerythropoietin receptor signaling pathway promotes growth and invasion abilities in human renal carcinoma cellserythropoietinerythropoietin受体信号通路促进经济增长和人类肾癌细胞入侵的能力.pdf

The Erythropoietin/Erythropoietin Receptor Signaling Pathway Promotes Growth and Invasion Abilities in Human Renal Carcinoma Cells 1 2 1 3 1 1 1 Pengjie Wu , Ning Zhang , Xi Wang , Chi Zhang , Teng Li , Xianghui Ning , Kan Gong * 1 Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing, People’s Republic of China, 2 Department of Urology, Beijing Chaoyang Hospital, Capital University of Medicine Science, Beijing, People’s Republic of China, 3 Department of General Surgery, Peking University First Hospital, Beijing, People’s Republic of China Abstract Co-expression of erythropoietin (Epo) and erythropoietin receptor (EpoR) has been found in various non-hematopoietic cancers including hereditary and sporadic renal cell carcinomas (RCC), but the Epo/EpoR autocrine and paracrine mechanisms in tumor progression have not yet been identified. In this study, we used RNA interference method to down- regulate EpoR to investigate the function of Epo/EpoR pathway in human RCC cells. Epo and EpoR co-expressed in primary renal cancer cells and 6 human RCC cell lines. EpoR signaling was constitutionally phosphorylated in primary renal cancer cells, 786-0 and Caki-1 cells, and recombinant human Epo (rhEpo) stimulation had no significant effects on further phosphorylation of EpoR pathway, proliferation, and invasiveness of the cells. Down-regulation of EpoR expression in 786- 0 cells by lentivirus-introduced siRNA resulted in inhibition of growth and invasiveness in vitro and in vivo, and promotion of cell apoptosis. In addition, rhEpo stimulation slightly antagonized the anti-tumor effect of Sunitinib on 786-0 cells. Sunit