Significance of glucocorticoid signaling in triple-negative breast cancer patients: a newly revealed interaction with androgen signaling
Autor: | Fouzia Guestini, Yasuaki Sagara, Ayako Kanai, Yoshiaki Rai, Erina Iwabuchi, Maki Tanaka, Yasuhiro Miki, Takanori Ishida, Freeha Khalid, Hironobu Sasano, Rin Yamaguchi, Yasuyo Ohi, Keely May McNamara, Minoru Miyashita, Yoshiaki Onodera |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cancer Research medicine.drug_class Triple Negative Breast Neoplasms 03 medical and health sciences Receptors Glucocorticoid 0302 clinical medicine Glucocorticoid receptor Breast cancer Cell Line Tumor Biomarkers Tumor medicine Humans RNA Messenger Glucocorticoids Triple-negative breast cancer Cell Proliferation Cell growth business.industry Androgen medicine.disease Immunohistochemistry Androgen receptor 030104 developmental biology Oncology Receptors Androgen 030220 oncology & carcinogenesis Dihydrotestosterone Androgens Cancer research Female business Biomarkers hormones hormone substitutes and hormone antagonists Glucocorticoid Protein Binding Signal Transduction medicine.drug |
Zdroj: | Breast Cancer Research and Treatment. 180:97-110 |
ISSN: | 1573-7217 0167-6806 |
Popis: | Chemotherapy is the only current effective systemic treatment for triple-negative breast cancer (TNBC) patients. Therefore, the identification of active biological pathways that could become therapeutic targets is crucial. In this study, considering the well-reported biological roles of glucocorticoid and androgen receptors (GR, AR) in TNBC, we attempted to explore the effects of glucocorticoids (GCs) on cell kinetics as well as the potential interaction between GR and AR in TNBC. We first explored the association between the status of GR, AR, and/or GCs-metabolizing enzymes such as 11β-hydroxysteroid dehydrogenase (11βHSD) 1 and 2 and the clinicopathological variables of the TNBC patients. Thereafter, we also studied the effects of dexamethasone (DEX) with/without dihydrotestosterone (DHT) on TNBC cell lines by assessing the cell proliferation, migration and GC response genes at the transcriptional level. GR positivity in carcinoma cells was significantly associated with adverse clinical outcome of the patients and AR positivity was significantly associated with lower histological grade and Ki-67 labeling index of the cases examined. In particular, AR positivity was significantly associated with decreased risks of developing recurrence in GR-positive TNBC patients. The subsequent in vitro studies revealed that DEX-promoted cell migration was inhibited by the co-treatment with DHT in GR/AR double-positive HCC38 cells. In addition, DHT inhibited the DEX-increased serum and glucocorticoid-regulated kinase-1 (SGK1) mRNA expression. This is the first study to reveal that the interaction of GR and AR did influence the clinical outcome of TNBC patients and GCs induced cell migration in TNBC cells. |
Databáze: | OpenAIRE |
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