Thyroid-Specific PPARγ Deletion Is Benign in the Mouse

Jingcheng Yu, Ronald J Koenig
Peroxisome proliferator–activated receptor g (PPARg) is widely expressed at low levels and regulates many physiological processes. In mice and humans, there is evidence that PPARg can function as a tumor suppressor. A PAX8-PPARg fusion protein (PPFP) is oncogenic in a subset of thyroid cancers, suggesting that inhibition of endogenous PPARg function by the fusion protein could contribute to thyroid oncogenesis. However, the function of PPARg within thyrocytes has never been directly tested. Therefore, we have created a thyroid-specific genetic knockout of murine Pparg and have studied thyroid biology in these mice. Thyroid size and histology, the expression of thyroid-specific genes, and serum T4 levels all are unaffected by loss of thyroidal PPARg expression. PPFP thyroid cancers have increased activation of AKT, and mice with thyroid- specific expression of PPFP combined with thyroid-specific loss of PTEN (a negative regulator of AKT) develop thyroid cancer. Therefore we createdmicewith combined thyroid-specific deletions of Pparg and Pten to test if there is oncogenic synergy between these deletions. Pten deletion alone results in benign thyroid hyperplasia, and this is unchanged when combined with deletion of Pparg. We conclude that, at least in the contexts studied, thyrocyte PPARg does not play a significant role in the development or function of the thyroid and does not function as a tumor suppressor.

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