The Warburg effect is genetically determined in inherited pheochromocytomas

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 b...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2009-09, Vol.4 (9), p.e7094-e7094
Main Authors: Favier, Judith, Brière, Jean-Jacques, Burnichon, Nelly, Rivière, Julie, Vescovo, Laure, Benit, Paule, Giscos-Douriez, Isabelle, De Reyniès, Aurélien, Bertherat, Jérôme, Badoual, Cécile, Tissier, Frédérique, Amar, Laurence, Libé, Rosella, Plouin, Pierre-François, Jeunemaitre, Xavier, Rustin, Pierre, Gimenez-Roqueplo, Anne-Paule
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aerobic respiration
Aged
Analysis
Angiogenesis
Bioinformatics
Cancer
Child
Dehydrogenases
Diabetes and Endocrinology/Adrenal Cortex
DNA microarrays
Electron Transport
Energy consumption
Energy use
Enzymes
Female
Gene expression
Gene mutation
Genes
Genes, p53 - genetics
Genetic aspects
Genetic disorders
Genomes
Germ-Line Mutation
Glucose metabolism
Glycolysis
Heart failure
Homeostasis
Humans
Hypertension
Hypoxia
Kidney cancer
Kinases
Male
Metabolic pathways
Middle Aged
Mitochondria
Mitochondria - metabolism
Mitochondrial DNA
Molecular Biology
Mutation
Neovascularization, Pathologic
Neuroendocrine tumors
Neurological disorders
Oligonucleotide Array Sequence Analysis
Oncology/Adrenal Cortex
Oxidative Phosphorylation
p53 Protein
Pheochromocytoma - genetics
Pheochromocytoma - physiopathology
Protein transport
Proteins
Thyroid gland
Transcription factors
Tumor proteins
Tumors
VHL protein
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0007094