Androgen and AR contribute to breast cancer development and metastasis: an insight of mechanisms.

Abstract	The role of androgen and androgen receptor (AR) in breast carcinogenesis has long been a disputed issue. This report provides a mechanistic insight into how androgen and AR contributes to invasion and metastasis of breast cancer. We find that dihydrotestosterone (DHT) is able to induce the epithelial-to-mesenchymal transition in breast cancer cells in an AR-dependent/estrogen receptor-independent manner. This process is dependent on the demethylation activity of lysine-specific demethylase 1A (LSD1) by epigenetically regulating the target genes E-cadherin and vimentin. In vivo, DHT promotes metastasis in a nude mouse model, and AR and LSD1 are indispensable in this process. We establish that higher expression of nucleus AR to cytoplasm AR associated with worse prognostic outcomes in breast cancer patient samples. This study maps an 'androgen-AR/LSD1-target genes' pathway in breast carcinogenesis, implicating the importance of hormonal balance in women, and the potential clinical significance of serum androgen and AR in prediction of breast cancer and selection of breast cancer therapy.
Authors	J Feng, L Li, N Zhang, J Liu, L Zhang, H Gao, G Wang, Y Li, Y Zhang, X Li, D Liu, J Lu, B Huang
Journal	Oncogene (Oncogene) Vol. 36 Issue 20 Pg. 2775-2790 (05 18 2017) ISSN: 1476-5594 [Electronic] England
PMID	27893717 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Androgens Cadherins Receptors, Androgen Receptors, Estrogen Vimentin Dihydrotestosterone Histone Demethylases KDM1A protein, human
Topics	Androgens (metabolism, pharmacology) Animals Breast Neoplasms (etiology, metabolism, mortality, pathology) Cadherins (genetics, metabolism) Cell Line, Tumor Cell Movement (drug effects) Cell Proliferation (drug effects) Dihydrotestosterone (metabolism, pharmacology) Disease Models, Animal Epithelial-Mesenchymal Transition (drug effects) Female Gene Expression Regulation (drug effects) Gene Knockdown Techniques Histone Demethylases (metabolism) Humans Mice Neoplasm Metastasis Prognosis Receptors, Androgen (genetics, metabolism) Receptors, Estrogen (metabolism) Signal Transduction (drug effects) Vimentin (genetics, metabolism) Xenograft Model Antitumor Assays

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