Inhibitory effects of peroxisome proliferator-activated receptor γ on thyroid carcinoma cell growth

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor involved in such cellular processes as adipogenesis, inflammation, atherosclerosis, cell cycle control, apoptosis, and carcinogenesis. PPARgamma gene mutations have been found in 4 of 55 sporadic colon cancers, and a chimeric PAX8-PPARgamma1 gene frequently generates a chromosomal translocation in thyroid follicular carcinomas, implicating PPARgamma in tumor suppression. We investigated whether PPARgamma is involved in the growth regulation of normal and tumor thyroid cells. We found no mutations in PPARgamma exons 3 and 5 in human thyroid carcinoma cell lines and tissues. Moreover, 1 cell line (NPA) of 6 analyzed did not express PPAR-gamma. Treatment of NPA with PPAR-gamma agonists did not induce any inhibitory effect. Conversely, PPARgamma agonists and PPARgamma overexpression led to a drastic reduction of the cell growth rate in PPARgamma-expressing thyroid carcinoma cells. Restoration of PPARgamma expression in NPA cells induced cell growth inhibition; PPARgamma agonists induced further inhibition. Growth inhibition induced by PPARgamma agonists or by PPARgamma gene overexpression. in thyroid carcinoma cells was associated with increased p27 protein levels and apoptotic cell death. Should these data be confirmed, PPAR-gamma could be a novel target for innovative therapy of thyroid carcinoma, particularly anaplastic carcinomas, which represent one of the most aggressive tumors in mankind and are unresponsive to conventional therapy.