Abstract
Chromosomal translocations that encode fusion oncoproteins have been observed consistently in leukemias/lymphomas and sarcomas but not in carcinomas, the most common human cancers. Here, we report that t(2;3)(q13;p25), a translocation identified in a subset of human thyroid follicular carcinomas, results in fusion of the DNA binding domains of the thyroid transcription factor PAX8 to domains A to F of the peroxisome proliferator-activated receptor (PPAR) gamma1. PAX8-PPARgamma1 mRNA and protein were detected in 5 of 8 thyroid follicular carcinomas but not in 20 follicular adenomas, 10 papillary carcinomas, or 10 multinodular hyperplasias. PAX8-PPARgamma1 inhibited thiazolidinedione-induced transactivation by PPARgamma1 in a dominant negative manner. The experiments demonstrate an oncogenic role for PPARgamma and suggest that PAX8-PPARgamma1 may be useful in the diagnosis and treatment of thyroid carcinoma.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma, Follicular / genetics*
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Adenocarcinoma, Follicular / metabolism
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Adenoma / genetics
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Adenoma / metabolism
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Adult
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Aged
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Carcinoma, Papillary / genetics
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Carcinoma, Papillary / metabolism
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Cell Line
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Cell Nucleus / metabolism
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Child
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / pharmacology
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DNA-Binding Proteins / physiology*
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Humans
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Middle Aged
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Nuclear Proteins*
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Oncogene Proteins, Fusion / chemistry
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Oncogene Proteins, Fusion / genetics
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Oncogene Proteins, Fusion / physiology*
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PAX8 Transcription Factor
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Paired Box Transcription Factors
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Receptors, Cytoplasmic and Nuclear / chemistry
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / physiology*
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Response Elements
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Thiazoles / pharmacology
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Thiazolidinediones*
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Thyroid Neoplasms / genetics*
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Thyroid Neoplasms / metabolism
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / pharmacology
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Trans-Activators / physiology*
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / pharmacology
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Transcription Factors / physiology*
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Transcription, Genetic
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Transcriptional Activation
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Translocation, Genetic
Substances
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DNA-Binding Proteins
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Nuclear Proteins
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Oncogene Proteins, Fusion
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PAX8 Transcription Factor
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PAX8 protein, human
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Paired Box Transcription Factors
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Receptors, Cytoplasmic and Nuclear
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Thiazoles
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Thiazolidinediones
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Trans-Activators
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Transcription Factors
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2,4-thiazolidinedione