title: Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc.
abstract: Unlike normal mammalian cells, which use oxygen to generate energy, cancer cells rely on glycolysis for energy and are therefore less dependent on oxygen. We previously observed that the c-Myc oncogenic transcription factor regulates lactate dehydrogenase A and induces lactate overproduction. We, therefore, sought to determine whether c-Myc controls other genes regulating glucose metabolism. In Rat1a fibroblasts and murine livers overexpressing c-Myc, the mRNA levels of the glucose transporter GLUT1, phosphoglucose isomerase, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase were elevated. c-Myc directly transactivates genes encoding GLUT1, phosphofructokinase, and enolase and increases glucose uptake in Rat1 fibroblasts. Nuclear run-on studies confirmed that the GLUT1 transcriptional rate is elevated by c-Myc. Our findings suggest that overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway.
authors.affiliation: Program in Human Genetics and Molecular Biology, Department of Medicine, and Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Osthus
authors.forename: H
authors.initials: H
authors.lastname: Shim
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: R
authors.initials: R
authors.lastname: Reddy
authors.forename: M
authors.initials: M
authors.lastname: Mukherjee
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: D
authors.initials: D
authors.lastname: Wonsey
authors.forename: L A
authors.initials: LA
authors.lastname: Lee
authors.forename: C V
authors.initials: CV
authors.lastname: Dang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts; D005786:Gene Expression Regulation; D016259:Genes, myc; D005947:Glucose / Q000235:genetics* / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D006019:Glycolysis / Q000235:genetics; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats
chemical_list: D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495679:Slc2a1 protein, rat; D005947:Glucose