title: B4GALT1 gene knockdown inhibits the hedgehog pathway and reverses multidrug resistance in the human leukemia K562/adriamycin-resistant cell line.
abstract: B4GALT1 gene encodes type II membrane-bound glycoprotein, named β-1, 4-galactosyltransferase 1 (β1, 4-Gal-T1), which can transfer galactose to acceptor sugars. B4GALT1 gene plays important roles in physiological process and disease development. In this study, we investigate the possible role and mechanism of B4GALT1 gene in multidrug resistance of human leukemia cell line. Significantly, higher expression of B4GALT1 was observed in adriamycin-resistant (ADR) K562 cell line (K562/ADR) than that in K562 cell line by real-time polymerase chain reaction and Western blotting. The activity of β1, 4-Gal-T1 enzyme, and Galβ-1,4GlcNAc structures on cell membrane glycoproteins was found at higher levels in K562/ADR cells than those in K562 cells. Further analysis of the B4GALT1 deregulation after using RNA interference approach showed that the silencing of B4GALT1 in K562/ADR cells resulted in increased sensitivity to chemotherapeutic drugs both in vitro and in vivo. The activity of the hedgehog signaling pathway affected the chemosensitivity of K562/ADR cells and was downregulated in K562/ADR cells with suppression of B4GALT1 gene. We hypothesize that B4GALT1 is responsible for the overcoming multidrug resistance in human leukemia therapy via regulating the activity of the hedgehog signaling pathway.
authors.affiliation: Department of Laboratory Medicine, College of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning Province, People's Republic of China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhou
authors.forename: Zhaohai
authors.initials: Z
authors.lastname: Zhang
authors.forename: Chunqing
authors.initials: C
authors.lastname: Liu
authors.forename: Changgong
authors.initials: C
authors.lastname: Jin
authors.forename: Jianing
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Miao
authors.forename: Li
authors.initials: L
authors.lastname: Jia
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005434:Flow Cytometry; D005700:Galactosyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007942:Leukemia, Experimental / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D053823:Hedgehog Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D004317:Doxorubicin; D005700:Galactosyltransferases; C119701:beta-1,4-galactosyltransferase I