The Warburg Effect Is Genetically Determined in Inherited Pheochromocytomas

被引：189

作者：

Favier, Judith

Briere, Jean-Jacques

Burnichon, Nelly

Riviere, Julie

Vescovo, Laure

Benit, Paule

Giscos-Douriez, Isabelle

De Reynies, Aurelien

Bertherat, Jerome

Badoual, Cecile

Tissier, Frederique

Amar, Laurence

Libe, Rosella

Plouin, Pierre-Francois

Jeunemaitre, Xavier

Rustin, Pierre

Gimenez-Roqueplo, Anne-Paule

机构：

[1] INSERM Unit 970, Paris

[2] Collège de France, Paris

[3] Université Paris Descartes, Faculté de Médecine, Paris

[4] Paris-Cardiovascular Research Center, HEGP, Paris

[5] INSERM Unit 676, Hôpital Robert Debré, Paris

[6] Université René Diderot, Faculté de Médecine, Paris

[7] Programme Cartes d'Identité des Tumeurs, Ligue Nationale Contre Le Cancer, Paris

[8] AP-HP, Hôpital Cochin, Département d'Endocrinologie, Paris

[9] AP-HP, Hôpital Européen Georges Pompidou, Service d'Anatomo-Pathologie, Paris

[10] AP-HP, Hôpital Cochin, Service d'Anatomie Pathologique, Paris

[11] AP-HP, Hôpital Européen Georges Pompidou, Service d'Hypertension Artérielle, Paris

[12] AP-HP, Hôpital Européen Georges Pompidou, Département de Génétique, Paris

[13] Rare Adrenal Cancer Network-Corticomédullo Surrénale Tumeur Endocrine, Institut National du Cancer, Paris

来源：

PLOS ONE | 2009年 / 4卷 / 09期

关键词：

D O I：

10.1371/journal.pone.0007094

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

共 43 条

[1] Genetic testing in pheochromocytoma or functional paraganglioma [J].

Amar, L ;

Bertherat, J ;

Baudin, E ;

Ajzenberg, C ;

Bressac-de Paillerets, B ;

Chabre, O ;

Chamontin, B ;

Delemer, B ;

Giraud, S ;

Murat, A ;

Niccoli-Sire, P ;

Richard, SP ;

Rohmer, V ;

Sadoul, JL ;

Strompf, L ;

Schlumberger, M ;

Bertagna, X ;

Plouin, PF ;

Jeunemaitre, X ;

Gimenez-Roqueplo, AP .

JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (34) :8812-8818

[2] Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas [J].

Amar, Laurence ;

Baudin, Eric ;

Burnichon, Nelly ;

Peyrard, Severine ;

Silvera, Stephane ;

Bertherat, Jerome ;

Bertagna, Xavier ;

Schlumberger, Martin ;

Jeunemaitre, Xavier ;

Gimenez-Roqueplo, Anne-Paule ;

Plouin, Pierre-Francois .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2007, 92 (10) :3822-3828

[3] Three spectrophotometric assays for the measurement of the five respiratory chain complexes in minuscule biological samples [J].

Benit, Paule ;

Goncalves, Sergio ;

Dassa, Emmanuel Philippe ;

Briere, Jean-Jacques ;

Martin, Gail ;

Rustin, Pierre .

CLINICA CHIMICA ACTA, 2006, 374 (1-2) :81-86

[4] TIGAR, a p53-inducible regulator of glycolysis and apoptosis [J].

Bensaad, Karim ;

Tsuruta, Atsushi ;

Selak, Mary A. ;

Calvo Vidal, M. Nieves ;

Nakano, Katsunori ;

Bartrons, Ramon ;

Gottlieb, Eyal ;

Vousden, Karen H. .

CELL, 2006, 126 (01) :107-120

[5] Mitochondrial succinate is instrumental for HIF1α nuclear translocation in SDHA-mutant fibroblasts under normoxic conditions [J].

Brière, JJ ;

Favier, J ;

Bénit, P ;

El Ghouzzi, V ;

Lorenzato, A ;

Rabier, D ;

Di Renzo, MF ;

Gimenez-Roqueplo, AP ;

Rustin, P .

HUMAN MOLECULAR GENETICS, 2005, 14 (21) :3263-3269

[6] Proteomic analysis of primary cell lines identifies protein changes present in renal cell carcinoma [J].

Craven, Rachel A. ;

Stanley, Anthea J. ;

Hanrahan, Sarah ;

Dods, James ;

Unwin, Richard ;

Totty, Nick ;

Hamden, Patricia ;

Eardley, Ian ;

Selby, Peter J. ;

Banks, Rosamonde E. .

PROTEOMICS, 2006, 6 (09) :2853-2864

[7] A HIF1α regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas [J].

Dahia, PLM ;

Ross, KN ;

Wright, ME ;

Hayashida, CY ;

Santagata, S ;

Barontini, M ;

Kung, AL ;

Sanso, G ;

Powers, JF ;

Tischler, AS ;

Hodin, R ;

Heitritter, S ;

Moore, F ;

Dluhy, R ;

Sosa, JA ;

Ocal, IT ;

Benn, DE ;

Marsh, DJ ;

Robinson, BG ;

Schneider, K ;

Garber, J ;

Arum, SM ;

Korbonits, M ;

Grossman, A ;

Pigny, P ;

Toledo, SPA ;

Nosé, V ;

Li, C ;

Stiles, CD .

PLOS GENETICS, 2005, 1 (01) :72-80

[8] Distinct gene expression profiles in norepinephrine- and epinephrine-producing hereditary and sporadic pheochromocytomas: activation of hypoxia-driven angiogenic pathways in von Hippel-Lindau syndrome [J].

Eisenhofer, G ;

Huynh, TT ;

Pacak, K ;

Brouwers, FM ;

Walther, MM ;

Linehan, WM ;

Munson, PJ ;

Mannelli, M ;

Goldstein, DS ;

Elkahloun, AG .

[9] Hereditary paraganglioma/pheochromocytoma and inherited succinate dehydrogenase deficiency [J].

Favier, J ;

Brière, JJ ;

Strompf, L ;

Amar, L ;

Filali, M ;

Jeunemaitre, X ;

Rustin, P ;

Gimenez-Roqueplo, AP .

HORMONE RESEARCH, 2005, 63 (04) :171-179

[10] Cloning and expression pattern of EPAS1 in the chicken embryo - Colocalization with tyrosine hydroxylase [J].

Favier, J ;

Kempf, H ;

Corvol, P ;

Gasc, JM .

FEBS LETTERS, 1999, 462 (1-2) :19-24

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