title: 5-Aza-2'-deoxycytidine increases sialyl Lewis X on MUC1 by stimulating β-galactoside:α2,3-sialyltransferase 6 gene.
abstract: Sialyl Lewis X is a tumor-associated antigen frequently found in the advanced cancers. However, the mechanism for the production of this cancer antigen is not entirely clear. The objective of this study is to examine whether epigenetics is involved in the regulation of the formation of this antigen. We observed an increase of sialyl Lewis X in HCT15 cells, a colon cancer cell line, treated with 5-Aza-2'-deoxycytidine. This treatment enhanced the expression of β-galactoside:α2,3-sialyltransferase 6 gene and sialyl Lewis X on MUC1, and the adherence of these cells to E-selectin under dynamic flow conditions. In addition, 5-Aza-2'-deoxycytidine treatment inhibited methylation of β-galactoside:α2,3-sialyltransferase 6 gene and siRNA knockdown of this gene drastically reduced sialyl Lewis X without affecting MUC1 expression. We conclude that 5-Aza-2'-deoxycytidine treatment increases sialyl Lewis X on MUC1 by stimulating the β-galactoside:α2,3-sialyltransferase 6 gene via inhibition of DNA methylation. Increased sialyl Lewis X by 5-Aza-2'-deoxycytidine raises a concern about the safety of this chemotherapeutic drug. In addition, β-galactoside:α2,3-sialyltransferase 6 gene may be a potential therapeutic target for suppressing tumorigenicity of colon cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA.
authors.forename: Vishwanath B
authors.initials: VB
authors.lastname: Chachadi
authors.forename: Helen
authors.initials: H
authors.lastname: Cheng
authors.forename: David
authors.initials: D
authors.lastname: Klinkebiel
authors.forename: Judith K
authors.initials: JK
authors.lastname: Christman
authors.forename: Pi-Wan
authors.initials: PW
authors.lastname: Cheng
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D019040:E-Selectin / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006003:Glycogen / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D055767:Immobilized Proteins / Q000378:metabolism; D008970:Molecular Weight; D018396:Mucin-1 / Q000378:metabolism*; D009844:Oligosaccharides / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen; D012799:Sialyltransferases / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D019040:E-Selectin; D004791:Enzyme Inhibitors; D055767:Immobilized Proteins; D018396:Mucin-1; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D000077209:Decitabine; D006003:Glycogen; D012799:Sialyltransferases; D001374:Azacitidine; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; C000722087:ST3GAL1 protein, human