Transcriptional profiling reveals coordinated up-regulation of oxidative metabolism genes in thyroid oncocytic tumors

被引:73
作者
Baris, O
Savagner, F
Nasser, V
Loriod, B
Granjeaud, S
Guyetant, S
Franc, B
Rodien, P
Rohmer, V
Bertucci, F
Birnbaum, D
Malthièry, Y
Reynier, P
Houlgatte, M
机构
[1] CHU Angers, INSERM, Epuipe Mixte INSERM Univ 0018, Lab Biochim & Biol Mol, F-49033 Angers, France
[2] CHU Angers, Serv Endocrinol Nutr & Med Interne, F-49033 Angers, France
[3] Inst J Paoli I Calmettes, Dept Mol Oncol, F-13273 Marseille, France
[4] INSERM, U119, F-13273 Marseille, France
[5] INSERM, Equipe Rech & Innovat Technol & Methodol 206, Lab Technol Avancees Genome & Clin, F-13009 Marseille, France
[6] Ctr Hosp Rech Univ, Anat Pathol Lab, F-37044 Tours, France
[7] Hop Ambroise Pare, Anat Pathol Lab, F-92104 Boulogne, France
关键词
D O I
10.1210/jc.2003-031238
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Oncocytomas are large cell tumors characterized by an abnormal proliferation of mitochondria. To investigate this phenomenon in thyroid oncocytomas, we determined gene expression profiles of 87 samples using microarrays of 6720 PCR products from cDNA clones. Samples included 29 thyroid oncocytomas and six papillary carcinomas, the remainder representing other thyroid pathologies or mitochondria-rich tumor samples, normal thyroid samples, and two thyroid cell lines. Hierarchical clustering and supervised analysis identified two specific oncocytic clusters and 163 distinctly regulated genes between oncocytoma and normal thyroid. Differential expression of five selected genes (APOD, BCL-2, COX, CTSB, and MAP2) was confirmed by immunohistochemistry. The two specific oncocytic clusters were rich in mitochondrial genes and revealed coordinated expression of nuclear and mitochondrial respiratory chain genes. We also observed the up-regulation of genes involved in mitochondrial biogenesis, such as nuclear respiratory factor 1 and the endothelial nitric oxide synthase. Several oxidative metabolism genes were overexpressed in oncocytomas, including those from the tricarboxylic acid cycle (MDH1) and cytosolic glycolysis (GAPD, ENO1, and GPI). On the contrary, the lactate dehydrogenase A gene, involved in anaerobic metabolism, was down-regulated. Our results suggest that, unlike a large number of solid tumors, thyroid oncocytomas produce energy through an aerobic pathway.
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收藏
页码:994 / 1005
页数:12
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