Low aerobic mitochondrial energy metabolism in poorly- or undifferentiated neuroblastoma

被引：63

作者：

Feichtinger, Rene' G. ^{[1
]}

Zimmermann, Franz ^{[1
]}

Mayr, Johannes A. ^{[1
]}

Neureiter, Daniel ^{[2
]}

Hauser-Kronberger, Cornelia ^{[2
]}

Schilling, Freimut H. ^{[3
]}

Jones, Neil ^{[1
]}

Sperl, Wolfgang ^{[1
]}

Kofler, Barbara ^{[1
]}

机构：

[1] Paracelsus Med Univ, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria

[2] Paracelsus Med Univ, Univ Hosp Salzburg, Dept Pathol, Salzburg, Austria

[3] Olga Hosp, Dept Pediat Oncol & Hematol, Stuttgart, Germany

来源：

BMC CANCER | 2010年 / 10卷

关键词：

TUMOR-SUPPRESSOR GENE; SULFUR PROTEIN BIOGENESIS; ENDOTHELIAL GROWTH-FACTOR; HIPPEL-LINDAU-DISEASE; RENAL-CELL CARCINOMA; ACTIVATING MUTATIONS; SOMATIC MUTATIONS; DNA MUTATIONS; ALK KINASE; COMPLEX-I;

D O I：

10.1186/1471-2407-10-149

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Succinate dehydrogenase (SDH) has been associated with carcinogenesis in pheochromocytoma and paraganglioma. In the present study we investigated components of the oxidative phosphorylation system in human neuroblastoma tissue samples. Methods: Spectrophotometric measurements, immunohistochemical analysis and Western blot analysis were used to characterize the aerobic mitochondrial energy metabolism in neuroblastomas (NB). Results: Compared to mitochondrial citrate synthase, SDH activity was severely reduced in NB (n = 14) versus kidney tissue. However no pathogenic mutations could be identified in any of the four subunits of SDH. Furthermore, no genetic alterations could be identified in the two novel SDH assembly factors SDHAF1 and SDH5. Alterations in genes encoding nfs-1, frataxin and isd-11 that could lead to a diminished SDH activity have not been detected in NB. Conclusion: Because downregulation of other complexes of the oxidative phosphorylation system was also observed, a more generalized reduction of mitochondrial respiration seems to be present in neuroblastoma in contrast to the single enzyme defect found in hereditary pheochromocytomas.

引用

页数：9

共 41 条

[1] A novel mutation of the RRM2B gene in an infant with early fatal encephalomyopathy, central hypomyelination, and tubulopathy [J].

Acham-Roschitz, Birgit ;

Plecko, Barbara ;

Lindbichler, Franz ;

Bittner, Reginald ;

Mache, Christoph J. ;

Sperl, Wolfgang ;

Mayr, Johannes A. .

MOLECULAR GENETICS AND METABOLISM, 2009, 98 (03) :300-304

[2] Investigation of the role of SDHB inactivation in sporadic phaeochromocytoma and neuroblastoma [J].

Astuti, D ;

Morris, M ;

Krona, C ;

Abel, F ;

Gentle, D ;

Martinsson, T ;

Kogner, P ;

Neumann, HPH ;

Voutilainen, R ;

Eng, C ;

Rustin, P ;

Latif, F ;

Maher, ER .

BRITISH JOURNAL OF CANCER, 2004, 91 (10) :1835-1841

[3] Severe depletion of mitochondrial DNA in spinal muscular atrophy [J].

Berger, A ;

Mayr, JA ;

Meierhofer, D ;

Fötschl, U ;

Bittner, R ;

Budka, H ;

Grethen, C ;

Huemer, M ;

Kofler, B ;

Sperl, W .

ACTA NEUROPATHOLOGICA, 2003, 105 (03) :245-251

[4] Role of human mitochondrial Nfs1 in cytosolic iron-sulfur protein biogenesis and iron regulation [J].

Biederbick, Annette ;

Stehling, Oliver ;

Roesser, Ralf ;

Niggemeyer, Brigitte ;

Nakai, Yumi ;

Elsaesser, Hans-Peter ;

Lill, Roland .

MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (15) :5675-5687

[5] Sporadic pheochromocytomas are rarely associated with germline mutations in the vhl tumor suppressor gene or the ret protooncogene [J].

Brauch, H ;

Hoeppner, W ;

Jähnig, H ;

Wöhl, T ;

Engelhardt, D ;

Spelsberg, F ;

Ritter, MM .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (12) :4101-4104

[6] Tricarboxylic acid cycle dysfunction as a cause of human diseases and tumor formation [J].

Briere, Jean-Jacques ;

Favier, Judith ;

Gimenez-Roqueplo, Anne-Paule ;

Rustin, Pierre .

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2006, 291 (06) :C1114-C1120

[7] Oncogenic mutations of ALK kinase in neuroblastoma [J].

Chen, Yuyan ;

Takita, Junko ;

Choi, Young Lim ;

Kato, Motohiro ;

Ohira, Miki ;

Sanada, Masashi ;

Wang, Lili ;

Soda, Manabu ;

Kikuchi, Akira ;

Igarashi, Takashi ;

Nakagawara, Akira ;

Hayashi, Yasuhide ;

Mano, Hiroyuki ;

Ogawa, Seishi .

NATURE, 2008, 455 (7215) :971-U56

[8] Transcription association of VHL and SDH mutations link hypoxia and oxidoreductase signals in pheochromocytomas [J].

Dahia, Patricia L. M. .

PHEOCHROMOCYTOMA, 2006, 1073 :208-220

[9] 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

[10] No evidence for involvement of SDHD in neuroblastoma pathogenesis -: art. no. 55 [J].

De Preter, K ;

Vandesompele, J ;

Hoebeeck, J ;

Vandenbroecke, C ;

Smet, J ;

Nuyts, A ;

Laureys, G ;

Combaret, V ;

Van Roy, N ;

Roels, F ;

Van Coster, R ;

Praet, M ;

De Paepe, A ;

Speleman, F .

BMC CANCER, 2004, 4 (1)

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