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The Journal of Clinical Endocrinology & Metabolism Vol. 87, No. 10 4728-4735
Copyright © 2002 by The Endocrine Society

Original Article

Inhibitory Effects of Peroxisome Proliferator-Activated Receptor {gamma} on Thyroid Carcinoma Cell Growth

Maria Luisa Martelli, Rodolfo Iuliano, Ilaria Le Pera, Irene Sama’, Carmen Monaco, Simona Cammarota, Todd Kroll, Lorenzo Chiariotti, Massimo Santoro and Alfredo Fusco

Dipartimento Medicina di Sperimentale e Clinica (M.L.M., R.I., I.L., I.S., L.C., A.F.), Facoltà di Medicina e Chirurgia di Catanzaro, Università di Catanzaro, 88100 Catanzaro, Italy; Dipartimento di Biologia e Patologia Cellulare e "Molecolare c/o Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche (C.M., S.C., M.S., A.F.), Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli Federico II", 80131 Naples, Italy; and 3Department of Pathology (T.K.), Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Alfredo Fusco, M.D., Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli, "Federico II", via Pansini 5, 80131 Naples, Italy. E-mail: afusco{at}napoli.com.

Abstract

Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) is a nuclear receptor involved in such cellular processes as adipogenesis, inflammation, atherosclerosis, cell cycle control, apoptosis, and carcinogenesis. PPAR{gamma} gene mutations have been found in 4 of 55 sporadic colon cancers, and a chimeric PAX8-PPAR{gamma}1 gene frequently generates a chromosomal translocation in thyroid follicular carcinomas, implicating PPAR{gamma} in tumor suppression. We investigated whether PPAR{gamma} is involved in the growth regulation of normal and tumor thyroid cells. We found no mutations in PPAR{gamma} 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, PPAR{gamma} agonists and PPAR{gamma} overexpression led to a drastic reduction of the cell growth rate in PPAR{gamma}-expressing thyroid carcinoma cells. Restoration of PPAR{gamma} expression in NPA cells induced cell growth inhibition; PPAR{gamma} agonists induced further inhibition. Growth inhibition induced by PPAR{gamma} agonists or by PPAR{gamma} 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.




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