title: The tumor promoting roles of erythropoietin/erythropoietin receptor signaling pathway in gastric cancer.
abstract: Erythropoietin (EPO), binding with its receptor (EPOR), plays an important role in erythropoiesis. EPOR is reported to be expressed in various non-hematopoietic cancers, including gastric cancer. Although recombinant human EPO (rhEPO) has been widely used clinically in anemia patients, it remains controversial whether it would promote tumor progression. In this study, we used siRNA interference method to downregulate EPOR expression to investigate the function of EPO/EPOR pathway in human gastric cancer cells. We found EPOR expressed significantly higher in gastric cancer tissues, and also in most gastric cancer cell lines. RhEPO promoted gastric cancer cell proliferation, migration in AGS cells, and promoted cells from G0/G1 stage to G2/M stage, but had no regulation on AGS cell apoptosis. Downregulation of EPOR expression by siRNA interference in AGS cells resulted in no significant effects on proliferation and invasiveness of the cells, but induced apoptosis (p < 0.05). Xenografted gastric tumor model was used to explore the effect of EPOR-overexpression on gastric cancer cells in vivo. Our result showed that overexpression of EPOR enhanced tumor formation in nude mice (p < 0.01). Our results suggest that EPO/EPOR pathway promotes gastric cancer formation, proliferation, migration, and decreases apoptosis.
authors.affiliation: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, 310016, China. ringwh@hotmail.com.|Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, 310016, China. ringwh@hotmail.com.
authors.forename: Weiling
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, 310016, China.|Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, 310016, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Zhinong
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, 310016, China.|Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, 310016, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, 310016, China.|Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, 310016, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, 310016, China.|Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, 310016, China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, 310016, China.|Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, 310016, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Dai
authors.affiliation: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, 310016, China. Jianmin_si@zju.edu.cn.|Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, 310016, China. Jianmin_si@zju.edu.cn.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Si
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D004921:Erythropoietin / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000473:pathology*
chemical_list: C554270:EPO protein, human; D017467:Receptors, Erythropoietin; D004921:Erythropoietin
keywords: Erythropoietin (EPO); Erythropoietin receptor (EPOR); Gastric cancer; Migration; Proliferation