Nuclear receptor expression in human differentiated thyroid tumors

Mond, Michael, Alexiadis, Maria, Eriksson, Natalie, Davis, Melissa J., Muscat, George E. O., Fuller, Peter J. and Gilfillan, Christopher (2014) Nuclear receptor expression in human differentiated thyroid tumors. Thyroid, 24 6: 1000-1011. doi:10.1089/thy.2013.0509

Author Mond, Michael
Alexiadis, Maria
Eriksson, Natalie
Davis, Melissa J.
Muscat, George E. O.
Fuller, Peter J.
Gilfillan, Christopher
Title Nuclear receptor expression in human differentiated thyroid tumors
Journal name Thyroid   Check publisher's open access policy
ISSN 1050-7256
Publication date 2014-06-01
Year available 2014
Sub-type Article (original research)
DOI 10.1089/thy.2013.0509
Open Access Status
Volume 24
Issue 6
Start page 1000
End page 1011
Total pages 12
Place of publication New Rochelle, NY, United States
Publisher Mary Ann Liebert
Language eng
Formatted 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.

Patients and 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 BRAFV600E 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 BRAFV600E and wild type BRAF PTC, provides a basis for further mechanistic studies and highlights potential novel therapeutic targets for this malignancy.
Keyword Endocrinology & Metabolism
Endocrinology & Metabolism
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
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Created: Thu, 22 May 2014, 21:20:01 EST by Susan Allen on behalf of Institute for Molecular Bioscience