机构：[1]Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA [2]Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA [3]Department of Pathology, UT MD Anderson Cancer Center, Houston, TX 77030, USA [4]Institute for Cancer Medicine, School of Basic Medical Sciences, and Department of Pathology, Xinan Medical University, Luzhou, Sichuan 646000, China [5]Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA [6]Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, Netherlands [7]Current address: College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi 710062, China [8]Current address: Departments of General Surgical Laboratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China 中山大学附属第一医院[9]Current address: Department of Data Science, University of Mississippi Medical Center, Jackson, MS 39216, USA
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.
基金：
Cancer Prevention and Research Institute of Texas grants RP120732 and RP150197 and NIH grants CA112403, CA193455 and CA160747. This study was also partially supported by Natural Science Foundation of China grants 81572619. The GEMC at BCM was partially supported by the National Institutes of Health (NIH) grant P30CA125123
第一作者机构：[1]Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA [7]Current address: College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi 710062, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA [4]Institute for Cancer Medicine, School of Basic Medical Sciences, and Department of Pathology, Xinan Medical University, Luzhou, Sichuan 646000, China
推荐引用方式(GB/T 7714)：
Hongmei Wu,Jiong Bi,Yan Peng,et al.Nuclear receptor NR4A1 is a tumor suppressor down-regulated in triple-negative breast cancer.[J].ONCOTARGET.2017,8(33):54364-54377.doi:10.18632/oncotarget.17532.
APA：
Hongmei Wu,Jiong Bi,Yan Peng,Lei Huo,Xiaobin Yu...&Jianming Xu.(2017).Nuclear receptor NR4A1 is a tumor suppressor down-regulated in triple-negative breast cancer..ONCOTARGET,8,(33)
MLA：
Hongmei Wu,et al."Nuclear receptor NR4A1 is a tumor suppressor down-regulated in triple-negative breast cancer.".ONCOTARGET 8..33(2017):54364-54377
