title: Critical involvement of the α(1,2)-fucosyltransferase in multidrug resistance of human chronic myeloid leukemia.
abstract: The fucosyltransferases are key enzymes in cell surface antigen synthesis during multidrug resistance (MDR) development. The aim of the present study was to analyze the alteration of α(1,2)-fucosyltransferase involved in MDR development in human chronic myeloid leukemia (CML). FUT1 was overexpressed in three CML/MDR cell lines and peripheral blood mononuclear cells (PBMC) of CML patients. However, no significant changes of FUT2 were observed. The altered levels of FUT1 had a significant impact on the phenotypic variation of MDR of K562 and K562/ADR cells, the activity of EGFR/MAPK pathway and P-glycoprotein (P-gp) expression. Blocking the EGFR/MAPK pathway by its specific inhibitor PD153035 or EGFR small interfering RNA (siRNA) resulted in the reduced MDR of K562/ADR cells. This study indicated that α(1,2)-fucosyltransferase involved in the development of MDR of CML cells probably through FUT1 regulated the activity of EGFR/MAPK signaling pathway and the expression of P-gp.
authors.affiliation: Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Che
authors.affiliation: College of Stomatology, Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Liye
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Sun
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D015536:Down-Regulation; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000378:metabolism; D005647:Fucosyltransferases / Q000502:physiology*; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D066246:ErbB Receptors; D005647:Fucosyltransferases; D020928:Mitogen-Activated Protein Kinases; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C512478:EGFR protein, human