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PPARγ insufficiency promotes follicular thyroid carcinogenesis via activation of the nuclear factor-κB signaling pathway

Oncogene volume 25, pages 2736–2747 (2006)Cite this article

Abstract

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

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Acknowledgements

We thank Dr Peter McPhie for the statistical analysis of the effect of rosiglitazone treatment on the pathological progression of TRβPV/PV mice. This research was supported, in part, by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

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Authors and Affiliations

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

    Y Kato, H Ying, L Zhao, F Furuya, O Araki & S-y Cheng

  2. Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    M C Willingham

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  1. Y Kato
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  2. H Ying
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  7. S-y Cheng
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Correspondence to S-y Cheng.

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Kato, Y., Ying, H., Zhao, L. et al. PPARγ insufficiency promotes follicular thyroid carcinogenesis via activation of the nuclear factor-κB signaling pathway. Oncogene 25, 2736–2747 (2006). https://doi.org/10.1038/sj.onc.1209299

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