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

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor involved in such cellular processes as adipogenesis, inflammation, atherosclerosis, cell cycle control, apoptosis, and carcinogenesis. PPARγ gene mutations have been found in 4 of 55 sporadic colon cancers, and a chimeric PAX8-PPARγ1 gene frequently generates a chromosomal translocation in thyroid follicular carcinomas, implicating PPARγ in tumor suppression. We investigated whether PPARγ is involved in the growth regulation of normal and tumor thyroid cells. We found no mutations in PPARγ exons 3 and 5 in human thyroid carcinoma cell lines and tissues. Moreover, 1 cell line (NPA) of 6 analyzed did not express PPARγ. Treatment of NPA with PPARγ agonists did not induce any inhibitory effect. Conversely, PPARγ agonists and PPARγ overexpression led to a drastic reduction of the cell growth rate in PPARγ-expressing thyroid carcinoma cells. Restoration of PPARγ expression in NPA cells induced cell growth inhibition; PPARγ agonists induced further inhibition. Growth inhibition induced by PPARγ agonists or by PPARγ gene overexpression in thyroid carcinoma cells was associated with increased p27 protein levels and apoptotic cell death. Should these data be confirmed, PPARγ 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.