Androgen receptor and heat shock protein 27 co-regulate the malignant potential of molecular apocrine breast cancer

Abstract

BackgroundThe most striking feature of molecular apocrine breast cancer (MABC) is the expression of androgen receptor (AR). We report here the mechanism of the AR in regulating the behavior of MABC.MethodsThe MABC cell line, MDA-MB-453, and the nonMABC cell line, MCF7, were used in this study. The effect of dihydrotestosterone (DHT) and heat shock protein 27 (HSP27) on cell proliferation was quantified using the cell counter kit-8 (CCK8) and clonogenic assays in vitro and by a xenograft tumor model in vivo. The expression of the AR and HSP27 was analyzed using western blot, qPCR, and immunofluorescence assays. Complexes of the AR and HSP27 were detected by co-immunoprecipitation (Co-IP).ResultsIn MDA-MB-453 cells, DHT promoted cell proliferation and stimulated AR and HSP27 translocation from the cytoplasm to the nucleus, whereas, it inhibited MCF7 cell growth, and only the AR translocated into the nucleus. HSP27 knock-down decreased the proliferative ability of MDA-MB-453 cells, which could be rescued by DHT, while HSP27 and DHT had synergistic effects on MCF7 cells. HSP27 phosphorylation was a prerequisite for AR translocation into the nucleus, especially phosphorylation on serine 82. In addition, DHT stimulated the tumorigenic and metastatic capacities of MDA-MB-453 cells, while HSP27 knock-down decreased the rate of tumor formation and induced apoptosis in cells.ConclusionsThe results suggest that HSP27 assists the AR in regulating the malignant behavior of MABC, and these findings might be helpful in the treatment of MABC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0762-y) contains supplementary material, which is available to authorized users.

Constitutively active androgen receptor supports the metastatic phenotype of endocrine-resistant hormone receptor-positive breast cancer

“…3 ). These findings present an additional regulatory control mechanism based on PTM to the canonical substrate-chaperone relationship between AR and Hsp27 established previously [ 27 , 38 ].…”

Constitutively Active Androgen Receptor Supports the Metastatic Phenotype of Endocrine-Resistant Hormone Receptor-Positive Breast Cancer

“…3). These findings present an additional regulatory control mechanism based on PTM to the canonical substratechaperone relationship between AR and Hsp27 established previously (27,38). AR agonist DHT stimulates transcription of mesenchymal genes and metastasis of MCF7 cells in xenograft studies (30).…”

circCUL2 regulates gastric cancer malignant transformation and cisplatin resistance by modulating autophagy activation via miR-142-3p/ROCK2

“…In breast cancer cells, the downregulation of ROCK2 changed the hardness of the extracellular matrix, which affects the chemosensitivity of tumor cells [44]. However, in pancreatic cancer and colon cancer, ROCK2 can promote the resistance of tumor cells to chemotherapy [45,46]. This research revealed that circCUL2 may affect the cisplatin sensitivity of GC cells by regulating miR-142-3p/ROCK2 by cotransfecting circCUL2 overexpression plasmids and miR-142-3p mimics.…”