title: Effect of ST3GAL 4 and FUT 7 on sialyl Lewis X synthesis and multidrug resistance in human acute myeloid leukemia.
abstract: Sialyl Lewis X (sLe X, CD15s) is a key antigen produced on tumor cell surfaces during multidrug resistance (MDR) development. The present study investigated the effect of α1, 3 fucosyltransferase VII (FucT VII) and α2, 3 sialyltransferase IV (ST3Gal IV) on sLe X oligosaccharides synthesis as well as their impact on MDR development in acute myeloid leukemia cells (AML). FUT7 and ST3GAL4 were overexpressed in three AML MDR cells and bone marrow mononuclear cells (BMMC) of AML patients with MDR by real-time polymerase chain reaction (PCR). A close association was found between the expression levels of FUT7 and ST3GAL4 and the amount of sLe X oligosaccharides, as well as the phenotypic variation of MDR of HL60 and HL60/ADR cells both in vitro and in vivo. Manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway, thereby regulating the proportionally mutative expression of P-glycoprotein (P-gp) and multidrug resistance related protein 1 (MRP1), both of which are known to be involved in MDR. Blocking the PI3K/Akt pathway by its specific inhibitor LY294002 or Akt short hairpin RNA (shRNA) resulted in the reduced MDR of HL60/ADR cells. This study indicated that sLe X involved in the development of MDR of AML cells probably through FUT7 and ST3GAL4 regulating the activity of PI3K/Akt signaling pathway and the expression of P-gp and MRP1.
authors: College of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning Province, China.
authors: Hongye
authors: H
authors: Ma
authors: Department of Microbiology, Dalian Medical University, Dalian, Liaoning Province, China.
authors: Huimin
authors: H
authors: Zhou
authors: Department of Bone Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China.
authors: Peng
authors: P
authors: Li
authors: Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
authors: Xiaobo
authors: X
authors: Song
authors: College of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning Province, China.
authors: Xiaoyan
authors: X
authors: Miao
authors: College of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning Province, China.
authors: Yanping
authors: Y
authors: Li
authors: College of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning Province, China. Electronic address: jiali@dlmedu.edu.cn.
authors: Li
authors: L
authors: Jia
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation; D002648:Child; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D005647:Fucosyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000080506:Sialyl Lewis X Antigen; D012799:Sialyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D055815:Young Adult; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005647:Fucosyltransferases; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009844:Oligosaccharides; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000080506:Sialyl Lewis X Antigen; D012799:Sialyltransferases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; C502597:FUT7 protein, human; C421109:multidrug resistance-associated protein 1; C000722087:ST3GAL1 protein, human
keywords: Acute myeloid leukemia cells; FUT7; MDR; ST3GAL4; sLe X