title: Peroxisome proliferator-activated receptor gamma is frequently downregulated in a diversity of sporadic nonmedullary thyroid carcinomas.
abstract: Peroxisome proliferator-activated receptor gamma (PPARgamma) 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 PPARgamma 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 PPARgamma expression in 13 of 17 (76%) nontranslocation tumors. Immunohistochemical analysis of 142 thyroid tumors showed a statistically significant reduction in PPARgamma 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-PPARgamma translocation in FTCs may be lower than previously thought, functional downregulation of PPARgamma is a key event in multiple types of thyroid neoplasia and is a possible target for therapeutic intervention.
authors.affiliation: Human Cancer Genetics Program, The Ohio State University, Columbus, OH, USA.
authors.forename: Micheala A
authors.initials: MA
authors.lastname: Aldred
authors.forename: Carl
authors.initials: C
authors.lastname: Morrison
authors.forename: Oliver
authors.initials: O
authors.lastname: Gimm
authors.forename: Cuong
authors.initials: C
authors.lastname: Hoang-Vu
authors.forename: Ulf
authors.initials: U
authors.lastname: Krause
authors.forename: Henning
authors.initials: H
authors.lastname: Dralle
authors.forename: Sissy
authors.initials: S
authors.lastname: Jhiang
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
mesh_terms: D002277:Carcinoma / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D012313:RNA