title: Nuclear receptor expression in human differentiated thyroid tumors.
abstract: BACKGROUND
  Nuclear receptors (NRs) play a key role in endocrine signaling and metabolism and are important therapeutic targets in a number of hormone-dependent malignancies. Studies on the role of NRs in thyroid cancer are limited.
  
  
  OBJECTIVE
  The objective of the study was to examine systematically the expression of the 48 human NRs in a series of benign and malignant thyroid tissues. Within the papillary carcinoma cohort, we sought to determine if NR expression differed significantly by BRAF mutation status.
  
  
  METHODS
  RNA was isolated from multinodular goiter (MNG; n=6), papillary carcinoma (PTC, n=14), follicular carcinoma (FC; n=5), and Hürthle cell carcinoma (HCC; n=7). The 48 human NRs were profiled in this panel by quantitative real time polymerase chain reaction. Protein expression for selected NRs (Rev-erbα and LXR-β) was examined by immunohistochemistry (IHC) on tissue microarrays comprising benign and malignant thyroid tissues.
  
  
  RESULTS
  Across all groups of benign and malignant thyroid tissue, there was prominent expression of LXR-β and ROR-γ. Key findings in PTC were marked overexpression of RXR-γ and Rev-erbα compared to MNG. Within the PTC cohort, when BRAF(V600E) tumors were compared with wild type BRAF, there was relative upregulation of RXR-γ and Rev-erbα and downregulation of AR, ERR-γ, and ROR-γ. In FC, EAR-2 was overexpressed, while PPAR-α and PPAR-δ were underexpressed compared to MNG. The NR expression profile of HCC was distinct, characterized by significant downregulation of a wide range of NRs. IHC for Rev-erbα and LXR-β localized protein expression to the tumor cells. Moderate to strong Rev-erbα immunostaining was seen in 22 out of 23 PTC, and, overall, staining was stronger than in the benign group.
  
  
  CONCLUSIONS
  These results represent the first systematic examination of NR expression in thyroid cancer. Our finding of tumor-specific patterns of NR expression, as well as significant differences in NR expression between BRAF(V600E) and wild type BRAF PTC, provides a basis for further mechanistic studies and highlights potential novel therapeutic targets for this malignancy.
authors.affiliation: 1 Prince Henry's Institute of Medical Research , Clayton, Australia .
authors.forename: Michael
authors.initials: M
authors.lastname: Mond
authors.forename: Maria
authors.initials: M
authors.lastname: Alexiadis
authors.forename: Natalie
authors.initials: N
authors.lastname: Eriksson
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Davis
authors.forename: George E O
authors.initials: GE
authors.lastname: Muscat
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Fuller
authors.forename: Christopher
authors.initials: C
authors.lastname: Gilfillan
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics; D018249:Adenoma, Oxyphilic; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000473:pathology / Q000503:physiopathology*; D002454:Cell Differentiation; D005260:Female; D006044:Goiter, Nodular / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000473:pathology / Q000503:physiopathology*; D059467:Transcriptome
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D048493:Proto-Oncogene Proteins B-raf