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Oncogene. 2006 May 4;25(19):2736-47.

PPARgamma insufficiency promotes follicular thyroid carcinogenesis via activation of the nuclear factor-kappaB signaling pathway.

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  • 1Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA.


The molecular genetic events underlying thyroid carcinogenesis are poorly understood. Mice harboring a knock-in dominantly negative mutant thyroid hormone receptor beta (TRbetaPV/PV mouse) spontaneously develop follicular thyroid carcinoma similar to human thyroid cancer. Using this mutant mouse, we tested the hypothesis that the peroxisome proliferator-activated receptor gamma (PPARgamma) could function as a tumor suppressor in thyroid cancer in vivo. Using the offspring from the cross of TRbetaPV/+ and PPARgamma+/- mice, we found that thyroid carcinogenesis progressed significantly faster in TRbetaPV/PV mice with PPARgamma insufficiency from increased cell proliferation and reduced apoptosis. Reduced PPARgamma protein abundance led to the activation of the nuclear factor-kappaB signaling pathway, resulting in the activation of cyclin D1 and repression of critical genes involved in apoptosis. Treatment of TRbetaPV/PV mice with a PPARgamma agonist, rosiglitazone, delayed the progression of thyroid carcinogenesis by decreasing cell proliferation and activation of apoptosis. These results suggest that PPARgamma is a critical modifier in thyroid carcinogenesis and could be tested as a therapeutic target in thyroid follicular carcinoma.

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