Mutant Thyroid Hormone Receptor Represses the Expression and Transcriptional Activity of Peroxisome Proliferator-activated Receptor during Thyroid Carcinogenesis
نویسندگان
چکیده
The molecular genetics underlying thyroid carcinogenesis is not clear. Recent identification of a PAX8-peroxisome proliferator-activated receptor (PPAR ) fusion gene in human thyroid follicular carcinoma suggests a tumor suppressor role of PPAR in thyroid carcinogenesis. Mice harboring a knockin mutant thyroid hormone receptor (TR PV) spontaneously develop thyroid follicular carcinoma through pathological progression of hyperplasia, capsular invasion, vascular invasion, anaplasia, and eventually, distant organ metastasis. This mutant mouse (TR PV/PV mouse) provides an unusual opportunity to ascertain the role of PPAR in thyroid carcinogenesis. Here, we show that the expression of PPAR mRNA was repressed in the thyroid gland of mutant mice during carcinogenesis. In addition, TR PV acted to abolish the ligand (troglitazone)-mediated transcriptional activity of PPAR . These results indicate that repression of PPAR expression and its transcriptional activity are associated with thyroid carcinogenesis and raise the possibility that PPAR could be tested as a therapeutic target in thyroid follicular carcinoma.
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