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Thyroid hormone receptors are tumor suppressors in a mouse model of metastatic follicular thyroid carcinoma

Oncogene volume 29, pages 1909–1919 (2010)Cite this article

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Abstract

Aberrant expression and mutations of thyroid hormone receptor genes (TRs) are closely associated with several types of human cancers. To test the hypothesis that TRs could function as tumor suppressors, we took advantage of mice with deletion of all functional TRs (TRα1−/−TRβ−/− mice). As these mice aged, they spontaneously developed follicular thyroid carcinoma with pathological progression from hyperplasia to capsular invasion, vascular invasion, anaplasia and metastasis to the lung, similar to human thyroid cancer. Detailed molecular analysis revealed that known tumor promoters such as pituitary tumor-transforming gene were activated and tumor suppressors such as peroxisome proliferator-activated receptor γ and p53 were suppressed during carcinogenesis. In addition, consistent with the human cancer, AKT–mTOR–p70S6K signaling and vascular growth factor and its receptor were activated to facilitate tumor progression. This report presents in vivo evidence that functional loss of both TRα1 and TRβ genes promotes tumor development and metastasis. Thus, TRs could function as tumor suppressors in a mouse model of metastatic follicular thyroid cancer.

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Acknowledgements

This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. We thank Drs H Ying and Y Kato for the analyses of survival curves and thyroid growth in the early phase of the present work.

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

    X-G Zhu, L Zhao & S-Y Cheng

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

    M C Willingham

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  1. X-G Zhu
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Correspondence to S-Y Cheng.

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Zhu, XG., Zhao, L., Willingham, M. et al. Thyroid hormone receptors are tumor suppressors in a mouse model of metastatic follicular thyroid carcinoma. Oncogene 29, 1909–1919 (2010). https://doi.org/10.1038/onc.2009.476

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