TY - JOUR
T1 - The Warburg effect is genetically determined in inherited pheochromocytomas
AU - Favier, Judith
AU - Brière, Jean Jacques
AU - Burnichon, Nelly
AU - Rivière, Julie
AU - Vescovo, Laure
AU - Benit, Paule
AU - Giscos-Douriez, Isabelle
AU - De Reyniès, Aurélien
AU - Bertherat, Jérôme
AU - Badoual, Cécile
AU - Tissier, Frédérique
AU - Amar, Laurence
AU - Libé, Rosella
AU - Plouin, Pierre François
AU - Jeunemaitre, Xavier
AU - Rustin, Pierre
AU - Gimenez-Roqueplo, Anne Paule
PY - 2009/9/18
Y1 - 2009/9/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70349472696&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0007094
DO - 10.1371/journal.pone.0007094
M3 - Article
C2 - 19763184
AN - SCOPUS:70349472696
SN - 1932-6203
VL - 4
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - e7094
ER -