B4GALT family mediates the multidrug resistance of human leukemia cells by regulating the hedgehog pathway and the expression of p-glycoprotein and multidrug resistance-associated protein 1.

Abstract

β-1, 4-Galactosyltransferase gene (B4GALT) family consists of seven members, which encode corresponding enzymes known as type II membrane-bound glycoproteins. These enzymes catalyze the biosynthesis of different glycoconjugates and saccharide structures, and have been recognized to be involved in various diseases. In this study, we sought to determine the expressional profiles of B4GALT family in four pairs of parental and chemoresistant human leukemia cell lines and in bone marrow mononuclear cells (BMMC) of leukemia patients with multidrug resistance (MDR). The results revealed that B4GALT1 and B4GALT5 were highly expressed in four MDR cells and patients, altered levels of B4GALT1 and B4GALT5 were responsible for changed drug-resistant phenotype of HL60 and HL60/adriamycin-resistant cells. Further data showed that manipulation of these two gene expression led to increased or decreased activity of hedgehog (Hh) signaling and proportionally mutative expression of p-glycoprotein (P-gp) and MDR-associated protein 1 (MRP1) that are both known to be related to MDR. Thus, we propose that B4GALT1 and B4GALT5, two members of B4GALT gene family, are involved in the development of MDR of human leukemia cells, probably by regulating the activity of Hh signaling and the expression of P-gp and MRP1.

• Authors: H Zhou, H Ma, W Wei, D Ji, X Song, J Sun, J Zhang, L Jia
• Journal: Cell death & disease (Cell Death Dis) Vol. 4 Pg. e654 (Jun 06 2013) ISSN: 2041-4889 [Electronic] England
• PMID: 23744354 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antibiotics, Antineoplastic
• Hedgehog Proteins
• Multidrug Resistance-Associated Proteins
• Doxorubicin
• Galactosyltransferases
• beta-1,4-galactosyltransferase I
• beta-1,4-galactosyltransferase V
• multidrug resistance-associated protein 1

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics, metabolism)
• Animals
• Antibiotics, Antineoplastic (pharmacology)
• Doxorubicin (pharmacology)
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Female
• Galactosyltransferases (physiology)
• Gene Expression
• Gene Expression Regulation, Neoplastic
• HL-60 Cells
• Hedgehog Proteins (metabolism)
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, metabolism, pathology)
• Leukemia, Myeloid, Acute (drug therapy, metabolism, pathology)
• Male
• Mice, Nude
• Middle Aged
• Multidrug Resistance-Associated Proteins (genetics, metabolism)
• Signal Transduction
• Tumor Burden
• Up-Regulation
• Xenograft Model Antitumor Assays