Abstract:Objective: To detect recombinant human erythropoietin(rh-EPO) on the biological behavior of tumor cells such as proliferation, apoptosis and metastasis; and to explore the role of EPO and EPO receptor(EPO-R) in the development of breast cancer.Methods: The expression levels of EPO and EPOR in MCF-7 and MDAMB-231 were detected by RT-PCR,immunocytochemistry and Western blotting. The proliferation abilities of MCF-7 and MDA-MB-231 cells interfered by rh-EPO in different concentration were detected by MTT assay.The Apoptosis of MCF-7 and MDA-MB-231 cells were evaluated by the terminal deoxynucleotidyl transferase mediated dutp-Biotin nick endlabeling assay(TUNEL).The migration and invasion abilities of MCF-7 and MDA-MB-231 cells were investigated by transwell technique. Results: The results of RT-PCR and Western blotting showed that EPO and EPO-R were expressed in MCF-7 and MDA-MB-231.The MTT assay and invasion assay revealed that rh-EPO could enhance the capacity of proliferation and the ability of migration and Matrigel-invasion in vitro both in MCF-7 and MDA-MB-231 cell lines in a time and dose-dependent manner. In TUNEL, the results showed that rh-EPO failed to prevent apoptosis. Conclusion: rh-EPO could enhance the capacity of proliferation and the ability of migration and Matrigel-invasion in vitro both in MCF-7 and MDA-MB-231 cell lines, and the effect on MCF-7 cells was better than that on MDA-MB-231 cells, but could not induce cell apoptosis.
收稿日期: 2013-01-02
基金资助:
福建省自然科学基金资助项目(2009J01155)
作者简介: 晋雯(1969—),女,福建福州人,副教授,硕士生导师,主要从事肿瘤病理学研究。
引用本文:
晋雯,张小容,孔令英. 促红细胞生成素在人乳腺癌细胞株中的表达及作用[J]. 江苏大学学报:医学版, 2013, 23(2): 124-129.
JIN Wen,ZHANG Xiao-rong, KONG Ling-ying.
Expression and function of erythropoietin in human breast cancer cell lines. Journal of Jiangsu University(Medicine Edition), 2013, 23(2): 124-129.
[1]Bennett CL, Silver SM, Djulbegovic B, et al. Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancerassociated anemia[J].JAMA,2008,299(8):914-924.[2]Wincewicz A, Sulkowska M, Koda M,et al. STAT3, HIF1α, EPO and EPORsignaling proteins in human primary ductal breast cancers[J].Folia Histochem Cytobiol,2007,45(2):81-86.[3]Jeong JY, Feldman L, Solar P,et al.Characterization of erythropoietin receptor and erythropoietin expression and function in human ovarian cancer cells[J]. Int J Cancer, 2008, 122(2): 274-280.[4]Arcasoy MO, Jiang X, Haroon ZA. Expression of erythropoietin receptor splice variants in human cancer[J]. Biochem Biophys Res Commun,2003,307(4): 999-1007.[5]Leo C, Horn LC, Rauscher C, et al. Expression of erythropoietin and erythropoietin receptor in cervical cancer and relationship to survival, hypoxia, and apoptosis[J]. Clin Cancer Res, 2006, 12(23): 6894-6900.[6]Li HG, Li JS, Chen WL, et al. Prognostic significance of erythropoietin and erythropoietin receptor in tongue squamous cell carcinoma[J]. Br J Oral Maxillofac Surg, 2009,47(6):470-475.[7]Küster O, Simon P, Mittelbronn M. et al. Erythropoietin receptor is expressed in meningiomas and lower levels are associated with tumour recurrence[J]. Neuropathol Appl Neurobiol, 2009,35(6):555-565.[8]Giatromanloaki A,Fiska A, Pitsiava D, et al. Erythropoietin receptor in endometrial carcinoma as related to HIF1α and VEGF expression[J].In Vivo,2009,23(5):699-703.[9]Yasuda Y, Hara S, Hirohata T, et al. Erythropoietinresponsive sites in normal and malignant human lung tissues[J].Anat Sci Int,2010,85(4):204-213.[10]Peres EA,Valable S,Guillamo JS,et al. Targeting the erythropoietin receptor on glioma cells reduces tumour growth[J]. Exp Cell Res, 2011, 317(16):2321-2332. [11]Mirmohammadsadegh A, Marini A, Gustrau A, et al. Role of erythropoietin receptor expression in malignant melanoma[J]. J Invest Dermatol, 2010, 130(1):201-210.[12]李勇,张景辉,龙跃平.促红细胞生成素对人乳腺癌细胞株MCF-7增殖的影响[J].武汉大学学报:医学版,2006,27(4):429-432.[13]Sinclair AM, CoxonA, Mccaffery L, et al. Functional erythropoietin receptor is undetectable in endothelial, cardiac, neuronal, and renal cells[J]. Blood, 2010, 115(21):4264-4272. [14]Abhold E, Rahimy E, WangRodriguez J, et al. Recombinant human erythropoietin promotes the acquisition of a malignant phenotype in head and neck squamous cell carcinoma cell lines in vitro[J].BMC Res Notes,2011,4:553.[15]Lopez TV, Lappin TR, Maxwell P,et al. Autocrine/paracrine erythropoietin signalling promotes JAK/STAT-dependent proliferation of human cervical cancer cells[J].Int J Cancer,2011,129(11):2566-2576.[16]Hamadmad SN,Hohl RJ.Erythropoietin stimulates cancer cell migration and activates RhoA protein through a MAPK/Erk-dependent mechanism[J].J Pharmacol Exp Ther,2008, 324(3):1227-1233.