Abstract
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.
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Acknowledgements
We thank Christophe Savagner for the statistical analysis, and Kanaya Malkani for the critical reading of this paper. This work was supported by grants from the French Ministry of Research, the Institut National de la Santé et de la Recherche Médicale (INSERM) and the Academic Hospital of Angers and the University of Angers (PHRC 01-10).
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Baris, O., Mirebeau-Prunier, D., Savagner, F. et al. Gene profiling reveals specific oncogenic mechanisms and signaling pathways in oncocytic and papillary thyroid carcinoma. Oncogene 24, 4155–4161 (2005). https://doi.org/10.1038/sj.onc.1208578
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DOI: https://doi.org/10.1038/sj.onc.1208578
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