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Updated: Feb 23, 2026

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Nuclear receptor NR4A1 is a tumor suppressor down-regulated in triple-negative breast cancer
Hongmei Wu1,2, Jiong Bi1,3, Yan Peng4
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Abstract:
The nuclear receptor (NR) superfamily contains hormone-inducible transcription factors that regulate many physiological and pathological processes through regulating gene expression. NR4A1 is an NR family member that still does not have an identified endogenous ligand, and its role in cancer is also currently unclear and controversial. In this study, we aimed to define the expression profiles and specific role of NR4A1 in the highly malignant triple-negative breast cancer (TNBC), which still lacks available targeted therapies. Bioinformatic analysis revealed a decrease of NR4A1 mRNA expression in human TNBC samples. Semi-quantitative analysis of NR4A1 protein expression by immunohistochemistry also identified a progressive NR4A1 reduction during the development of mouse basal-like mammary tumors and a significant NR4A1 downregulation in human TNBC samples. Furthermore, the expression levels of NR4A1 in human TNBC were negatively associated with tumor stage, lymph node metastasis and disease recurrence. Moreover, ectopic expression of NR4A1 in MDA-MB-231, a TNBC cell line with little endogenous NR4A1, inhibited the proliferation, viability, migration and invasion of these cells, and these inhibitions were associated with an attenuated JNK1-AP-1-cyclin D1 pathway. NR4A1 expression also largely suppressed the growth and metastasis of these cell-derived tumors in mice. These results demonstrate that NR4A1 is downregulated in TNBC and restoration of NR4A1 expression inhibits TNBC growth and metastasis, suggesting that NR4A1 is a tumor suppressor in TNBC.
Insights
Nuclear receptor subfamily 4 group A member 1 (NR4A1) acts as a tumor suppressor in triple-negative breast cancer (TNBC). Its downregulation correlates with TNBC progression, and restoring NR4A1 inhibits cancer growth and metastasis.
Area of Science:
- Molecular biology
- Cancer research
- Endocrinology
Background:
- Nuclear receptors (NRs) are transcription factors regulating physiological processes.
- NR4A1's role in cancer is unclear, and triple-negative breast cancer (TNBC) lacks targeted therapies.
- NR4A1 lacks an identified endogenous ligand.
Purpose of the Study:
- To define NR4A1 expression profiles in TNBC.
- To elucidate the specific role of NR4A1 in TNBC progression and metastasis.
Main Methods:
- Bioinformatic analysis of NR4A1 mRNA expression in human TNBC samples.
- Semi-quantitative analysis of NR4A1 protein expression via immunohistochemistry in mouse and human samples.
- Ectopic expression of NR4A1 in TNBC cell lines and assessment of proliferation, viability, migration, and invasion.
- In vivo studies using cell-derived tumors in mice.
Main Results:
- NR4A1 mRNA and protein expression are significantly downregulated in human TNBC.
- NR4A1 downregulation correlates negatively with tumor stage, lymph node metastasis, and disease recurrence.
- Ectopic NR4A1 expression inhibited TNBC cell proliferation, viability, migration, and invasion, partly via the JNK1-AP-1-cyclin D1 pathway.
- NR4A1 suppressed tumor growth and metastasis in vivo.
Conclusions:
- NR4A1 is downregulated in TNBC, acting as a tumor suppressor.
- Restoration of NR4A1 expression inhibits TNBC growth and metastasis.
- NR4A1 represents a potential therapeutic target for TNBC.
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