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Peroxisome proliferator-activated receptor gamma is frequently downregulated in a diversity of sporadic nonmedullary thyroid carcinomas

Oncogene volume 22, pages 3412–3416 (2003)Cite this article

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) has previously been implicated in the pathogenesis of follicular thyroid carcinoma (FTC), where a translocation with PAX8 has been reported in some 50% of tumors in three small series. The resultant fusion protein inhibits normal PPARγ function by a dominant-negative mechanism. In a series of 19 FTCs, we identified this translocation in only two tumors (10.5%). However, microarray analysis and semiquantitative RT–PCR demonstrated greatly reduced PPARγ expression in 13 of 17 (76%) nontranslocation tumors. Immunohistochemical analysis of 142 thyroid tumors showed a statistically significant reduction in PPARγ immunoreactive protein, not only in FTCs but also in papillary thyroid carcinomas and Hurthle cell carcinomas. This suggests that while the overall frequency of the PAX8–PPARγ translocation in FTCs may be lower than previously thought, functional downregulation of PPARγ is a key event in multiple types of thyroid neoplasia and is a possible target for therapeutic intervention.

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Acknowledgements

We are grateful to core facility staff at The Ohio State University for their services: Kimberley Bentley and Yiwen Liu-Stratton for microarray hybridizations, Mike Stevens and Jenny Panescu for ABI genotyping and sequencing, and Susie Jones for immunohistochemistry. MAA is supported by an Advanced Training Fellowship from the Wellcome Trust, UK. CE is a recipient of the Doris Duke Distinguished Clinical Scientist Award. This work was partially funded by National Cancer Institute Grant P30CA16058 to The Ohio State University Comprehensive Cancer Center, and generous gifts from the Abrams family and the Brown family in memory of Welton D Brown (to CE).

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Authors and Affiliations

  1. Human Cancer Genetics Program, The Ohio State University, Columbus, OH, USA

    Micheala A Aldred, Carl Morrison & Charis Eng

  2. Clinical Cancer Genetics Program, The Ohio State University, Columbus, OH, USA

    Micheala A Aldred, Carl Morrison & Charis Eng

  3. Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

    Micheala A Aldred, Carl Morrison, Sissy Jhiang & Charis Eng

  4. Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA

    Carl Morrison & Charis Eng

  5. Department of Pathology, The Ohio State University, Columbus, OH, USA

    Carl Morrison

  6. Department of Surgery, Martin-Luther-Universitat, Halle-Wittenberg, Halle/Saale, Germany

    Oliver Gimm, Cuong Hoang-Vu & Henning Dralle

  7. Institute of Pathology, Martin-Luther-Universitat, Halle-Wittenberg, Halle/Saale, Germany

    Ulf Krause

  8. Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, USA

    Sissy Jhiang

  9. Division of Medical Genetics, University of Leicester, Leicester, UK

    Micheala A Aldred

  10. Cancer Research UK Human Cancer Genetics Research Group, University of Cambridge, Cambridge, UK

    Charis Eng

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  1. Micheala A Aldred
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  2. Carl Morrison
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Correspondence to Charis Eng.

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Aldred, M., Morrison, C., Gimm, O. et al. Peroxisome proliferator-activated receptor gamma is frequently downregulated in a diversity of sporadic nonmedullary thyroid carcinomas. Oncogene 22, 3412–3416 (2003). https://doi.org/10.1038/sj.onc.1206400

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