Related Experiment Video
Updated: May 2, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Nuclear receptor expression in human differentiated thyroid tumors
Michael Mond1, Maria Alexiadis, Natalie Eriksson
11 Prince Henry's Institute of Medical Research , Clayton, Australia .
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 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.
Insights
Nuclear receptors (NRs) show distinct expression patterns in thyroid cancers, differing between tumor types and BRAF mutation status. These findings reveal potential new therapeutic targets for endocrine malignancies.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Nuclear receptors (NRs) are crucial in endocrine signaling and metabolism.
- NRs are key therapeutic targets for hormone-dependent cancers.
- Limited research exists on NR roles in thyroid cancer.
Purpose of the Study:
- Systematically examine the expression of 48 human NRs in benign and malignant thyroid tissues.
- Investigate NR expression differences in papillary thyroid carcinoma (PTC) based on BRAF mutation status.
Main Methods:
- Quantitative real-time PCR profiled 48 human NRs in multinodular goiter (MNG), PTC, follicular carcinoma (FC), and Hürthle cell carcinoma (HCC).
- Immunohistochemistry (IHC) assessed protein expression of Rev-erbα and LXR-β.
- Tissue microarrays included benign and malignant thyroid tissues.
Main Results:
- LXR-β and ROR-γ were prominently expressed across all thyroid tissues.
- PTC showed overexpression of RXR-γ and Rev-erbα compared to MNG.
- BRAF(V600E) PTC exhibited altered NR expression (upregulation of RXR-γ, Rev-erbα; downregulation of AR, ERR-γ, ROR-γ) versus wild-type BRAF.
- FC displayed EAR-2 overexpression and PPAR-α/δ underexpression.
- HCC showed a distinct profile with widespread NR downregulation.
- IHC confirmed Rev-erbα and LXR-β protein localization in tumor cells, with stronger Rev-erbα staining in PTC.
Conclusions:
- This study provides the first systematic analysis of NR expression in thyroid cancer.
- Identified tumor-specific NR expression patterns and BRAF-dependent differences in PTC.
- These findings support further research into NR mechanisms and potential therapeutic applications in thyroid cancer.
Related Concept Videos
01:31Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
01:20Synthesis and Regulation of Thyroid Hormones
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
01:27Hyperthyroidism II: Pathophysiology
01:28Graves' Disease I: Introduction
01:08Intracellular Hormone Receptors
01:18Functions of Thyroid Hormones
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...