Gene profiling reveals specific oncogenic mechanisms and signaling pathways in oncocytic and papillary thyroid carcinoma.
The oncogenic pathways in mitochondrial-rich thyroid carcinomas are not clearly understood. To investigate the possible implication of mitochondrial abundance in the genesis of thyroid tumors, we have explored the gene expression profile of six oncocytic carcinomas and six mitochondrial-rich papillary carcinomas using cDNA-microarray technology. A supervised approach allowed us to identify 83 genes differentially expressed in the two types of carcinoma. These genes were classified according to their ontologic profiles. Three genes, NOS3, alpha-actinin-2 and alpha-catenin, suspected of playing a role in tumor genesis, were explored by quantitative RT-PCR analysis and immunohistochemistry. Of the 59 genes overexpressed in papillary carcinomas, 51% were involved in cell communication. Of the 24 genes overexpressed in oncocytic carcinomas, 84% were involved in mitochondrial and cellular metabolism. Our results suggest that mitochondrial respiratory chain complexes III and IV play a significant role in the regulation of reactive oxygen species production by oncocytic tumors.
Baris
Olivier
O
INSERM EMI-U 0018, Laboratoire de Biochimie et Biologie Moléculaire, CHU, 4 rue Larrey, Angers F-49033, France. oliver.baris@med.univ-angers.fr
Mirebeau-Prunier
Delphine
D
Savagner
Frédérique
F
Rodien
Patrice
P
Ballester
Benoit
B
Loriod
Béatrice
B
Granjeaud
Samuel
S
Guyetant
Serge
S
Franc
Brigitte
B
Houlgatte
Rémi
R
Reynier
Pascal
P
Malthiery
Yves
Y
D000185:Actinin / Q000235:genetics; D002277:Carcinoma / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics*; D002450:Cell Communication / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D019001:Nitric Oxide Synthase / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D009857:Oncogenes; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*; D051178:alpha Catenin
C495273:CTNNA1 protein, human; D003598:Cytoskeletal Proteins; D051178:alpha Catenin; D000185:Actinin; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III