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The Paired Box-8/Peroxisome Proliferator-Activated Receptor- Oncogene in Thyroid Tumorigenesis

Department of Medicine (H.V.R., B.M., N.L.E.), Division of Endocrinology, and Departments of Laboratory Medicine and Pathology (S.K.G.G.) and Biochemistry and Molecular Biology (N.L.E.), Mayo Clinic and Foundation, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Norman L. Eberhardt, Ph.D., Department of Medicine/Division of Endocrinology, 200 First Street SW, Mayo Clinic, Rochester, Minnesota 55905. E-mail: eberhardt{at}mayo.edu.

The American Cancer Society estimates 30,180 new cases of thyroid cancer in the United States in 2006. Of all thyroid cancers, 15–20% are follicular thyroid carcinoma (FTC), making this the second most common thyroid malignancy (after papillary carcinoma). A proportion of FTC has been found to be associated with a chromosomal translocation, t (2, 3)(q13;p25), which fuses the thyroid-specific transcription factor paired box-8 with the peroxisome proliferator-activated receptor- nuclear receptor, a ubiquitously expressed transcription factor. This fusion event causes expression of a paired box-8/peroxisome proliferator-activated receptor- fusion protein (PPFP). PPFP is detected in approximately 30% of FTC. In this report we review data on the role of PPFP in FTC, its mechanism of oncogenesis, and PPFP targeting as a strategy in thyroid cancer treatment.