Cross-Talk between Extracellular S1P/S1P2 and P42/44 MAPK in bcr/abl Positive Chronic Myeloid Leukemia Cells

作     者：Yin Xu Fei-qun Zheng Qun-wei Zhang Yang Liu Hai-feng Duan Chun-ping Cui Bin Wu Yi-de Qin 

作者机构：Deparment of Biochemistry and Molecular Biology Anhui Medical University Hefei 230032 China Department of Experimental Hematology Beijing Institute of Radiation Medicine Beijing 100850 China Key Laboratory of Carcinogenesis and Translational Research （Ministry of Education） Department of lnterventional Therapy Peking University School of Oncology Beijing Cancer Hospital ＆ Institute Beijing 100142 China 

出 版 物：《Chinese Journal of Cancer Research》 (中国癌症研究（英文版）)

年 卷 期：2009年第21卷第1期

页      面：20-27页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China (No. 30570782). 

主　　题：Sphingosine kinase Sphingosine 1-phosphate CML Extracellular signal-regulated kinase/mitogen-activated protein kinase Cross-talk 

摘      要：Objective： BCR/ABL oncoprotein-expression is associated with uncontrolled cell growth. Sphingosine kinase 1 （SPK1） regulates the production of sphingosine 1-phosphate （S1P）, a key lipid signal molecular in cell proliferation and survival. The objective of this study was to elucidate the roles of S1P and its receptors in bcr/abl positive chronic myeloid leukemia （CML） cells. Methods： The expressions of SIP receptors： S1P1, S1P2 and S1P3 in CML cells were detected by RT-PCR. SPK1 expression, activity and extracellular S1P were determined in ECV304 and HL-60 cells which were transfected with bcr/abl gene. To elucidate the relationship between the BCR/ABL, ERK/MAPK （extracellular signal-regulated kinase/mitogen-activated protein kinase）, SPK/S 1P and S 1P/S 1 P2 signal pathways, bcr/abl positive CML cell line K562 was treated with STI571, PD98059, N,N-dimethyl sphingosine （DMS） and JTE-013. Results： Retrovirus-mediated overexpression of bcr/abl gene in ECV304 and HL-60 cells resulted in upregulation of the expression, activity of SPK1 and increase of the secretion of SIP, whereas treatment of STI571 and PD98059 decreased the BCR/ABL-induced S1P secretion. Treatment of DMS reduced S1P secretion and P42/44MAPK phosphorylation. S1P2-selective antagonist JTE-013 could also decrease P42/44MAPK phosphorylation. Conclusion： These results suggest that BCR/ABL up-regulates extracellular sphingosine 1-phosphate through sphingosine kinase 1 and there is cross-talk between SPK1/S1P/S1P2 and P42/44MAPK in bcr/abl positive CML cells.