scholarly journals Estrogen-Related Receptor α (ERRα) and G Protein-Coupled Estrogen Receptor (GPER) Synergistically Indicate Poor Prognosis in Patients with Triple-Negative Breast Cancer

2020 ◽  
Vol Volume 13 ◽  
pp. 8887-8899
Author(s):  
Shuang Ye ◽  
Yuanyuan Xu ◽  
Ling Wang ◽  
Kewen Zhou ◽  
Jiehua He ◽  
...  
2017 ◽  
Vol 43 (5) ◽  
pp. 2047-2061 ◽  
Author(s):  
Yan Shen ◽  
Fang Yang ◽  
Wenwen Zhang ◽  
Wei Song ◽  
Yuxiu Liu ◽  
...  

Background/Aims: The targeted therapy for triple-negative breast cancer (TNBC) is still challenging due to poor understanding on its molecular etiology. The androgen receptor (AR) has recently emerged as a prognostic and treatment-predictive marker in breast cancer. However, the role of AR in TNBC remained elusive. Methods: Immunohistochemistry (IHC) was used to detect AR and G-protein coupled estrogen receptor (GPER) expression in tissue microarrays of 165 TNBC patients. Microarray analysis of mRNAs was performed to identify downstream regulators of AR. TNBC cells were cultured with dihydrotestosterone (DHT) alone or in combination with AR knockdown performed with AR shRNA. Cell viability and colony formation were assessed. Western blotting and qRT-PCR were used to examine protein and mRNA expression, respectively. The potential mechanism of AR-mediated GPER suppression was identified by Chromatin immunoprecipitation (ChIP) assay. AR and GPER expressions were also assessed in nude mouse xenografts by IHC. Results: IHC staining showed that the expression of AR was positively associated with tumor size, lymph node metastasis and high-grade tumor in TNBC patients. AR activation triggered by DHT suppressed GPER expression, to promote cell growth of TNBC. G-1, a GPER agonist, inhibited DHT-stimulated proliferation. Further experiments illustrated that AR suppressed GPER activation via binding directly to the promoter of GPER. Moreover, a negative correlation between AR and GPER was observed in MDA-MB-231 tumor cell xenografts and TNBC patient samples. Conclusions: The suppression of GPER via AR may be involved in the positive actions towards the TNBC progression, making it a promising therapeutic target for TNBC treatment.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Alexandra Blake ◽  
Magdalena Dragan ◽  
Rommel G. Tirona ◽  
Daniel B. Hardy ◽  
Muriel Brackstone ◽  
...  

2011 ◽  
Vol 128 (2) ◽  
pp. 457-466 ◽  
Author(s):  
Atanas Ignatov ◽  
Tanja Ignatov ◽  
Christine Weißenborn ◽  
Holm Eggemann ◽  
Joachim Bischoff ◽  
...  

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Susanne Schüler-Toprak ◽  
Julia Häring ◽  
Elisabeth C. Inwald ◽  
Christoph Moehle ◽  
Olaf Ortmann ◽  
...  

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