title: The Warburg effect is genetically determined in inherited pheochromocytomas.
abstract: The Warburg effect describes how cancer cells down-regulate their aerobic respiration and preferentially use glycolysis to generate energy. To evaluate the link between hypoxia and Warburg effect, we studied mitochondrial electron transport, angiogenesis and glycolysis in pheochromocytomas induced by germ-line mutations in VHL, RET, NF1 and SDH genes. SDH and VHL gene mutations have been shown to lead to the activation of hypoxic response, even in normoxic conditions, a process now referred to as pseudohypoxia. We observed a decrease in electron transport protein expression and activity, associated with increased angiogenesis in SDH- and VHL-related, pseudohypoxic tumors, while stimulation of glycolysis was solely observed in VHL tumors. Moreover, microarray analyses revealed that expression of genes involved in these metabolic pathways is an efficient tool for classification of pheochromocytomas in accordance with the predisposition gene mutated. Our data suggest an unexpected association between pseudohypoxia and loss of p53, which leads to a distinct Warburg effect in VHL-related pheochromocytomas.
authors.affiliation: INSERM, Unit 970, Paris, France. judith.favier@inserm.fr
authors.forename: Judith
authors.initials: J
authors.lastname: Favier
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Brière
authors.forename: Nelly
authors.initials: N
authors.lastname: Burnichon
authors.forename: Julie
authors.initials: J
authors.lastname: Rivière
authors.forename: Laure
authors.initials: L
authors.lastname: Vescovo
authors.forename: Paule
authors.initials: P
authors.lastname: Benit
authors.forename: Isabelle
authors.initials: I
authors.lastname: Giscos-Douriez
authors.forename: Aurélien
authors.initials: A
authors.lastname: De Reyniès
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.forename: Cécile
authors.initials: C
authors.lastname: Badoual
authors.forename: Frédérique
authors.initials: F
authors.lastname: Tissier
authors.forename: Laurence
authors.initials: L
authors.lastname: Amar
authors.forename: Rosella
authors.initials: R
authors.lastname: Libé
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Plouin
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaitre
authors.forename: Pierre
authors.initials: P
authors.lastname: Rustin
authors.forename: Anne-Paule
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004579:Electron Transport; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D018095:Germ-Line Mutation; D006019:Glycolysis; D006801:Humans; D000860:Hypoxia; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation; D010673:Pheochromocytoma / Q000235:genetics* / Q000503:physiopathology*