title: Effects of treatment with androgen receptor ligands on microRNA expression of prostate cancer cells.
abstract: Post-transcriptional regulation by microRNA (miRNA) is an important aspect of androgen receptor (AR) signalling in prostate cancer cells. However, the global profiling of miRNA expression in prostate cancer cells following treatment with AR ligands has not been reported so far. In this study we examined the effect of treatment with two AR agonists (mibolerone (MIB) and dihydrotestosterone (DHT)) and an AR antagonist (bicalutamide (BIC)) on miRNA expression in the human androgen-dependent LNCaP prostate cancer cell line using microarray technology and verification of selected miRNA using quantitative real-time PCR (qRT-PCR). No miRNA was identified as differentially expressed following treatment with the AR antagonist BIC. In contrast, a number of common and compound-specific alterations in miRNA expression were observed following treatment with AR agonists. Unexpectedly it was found that treatment with the AR agonists resulted in the repression of miR-221, a miRNA previously established to be involved with prostate cancer development. This observation indicates that this miRNA may have a more complex role in prostate cancer development than considered previously. Treatment with MIB led to an induction of miR-210 expression, a hypoxia-related miRNA. This miRNA is reported to be involved in cell adaptation to hypoxia and thus induction in conditions of normoxia may be important in driving metabolic changes observed in prostate cancer. Thus examining the effect of AR agonists and antagonists on miRNA expression can provide novel insights into the response of cells to AR ligands and subsequent downstream events.
authors.affiliation: Department of Surgery & Cancer, Biomolecular Medicine, Imperial College London, London SW72AZ, UK.
authors.forename: Corrinne V
authors.initials: CV
authors.lastname: Segal
authors.affiliation: Department of Cytogenetics and Genomics, Cyprus Institute of Neurology and Genetics, Cyprus.
authors.forename: Costas
authors.initials: C
authors.lastname: Koufaris
authors.affiliation: GlaxoSmithKline, Ware, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Powell
authors.affiliation: Department of Surgery & Cancer, Biomolecular Medicine, Imperial College London, London SW72AZ, UK. Electronic address: n.gooderham@imperial.ac.uk.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Gooderham
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D008024:Ligands; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009277:Nandrolone / Q000031:analogs & derivatives / Q000494:pharmacology; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014105:Tosyl Compounds / Q000494:pharmacology
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D013196:Dihydrotestosterone; D007610:Kallikreins; D008024:Ligands; D035683:MicroRNAs; D009277:Nandrolone; D009570:Nitriles; D017430:Prostate-Specific Antigen; D011944:Receptors, Androgen; D014105:Tosyl Compounds; C410798:AR protein, human; C543800:MIRN210 microRNA, human; C525709:MIR221, human; C100075:mibolerone; C053541:bicalutamide; C549870:KLK3 protein, human
keywords: Androgen agonist; Androgen antagonist; Prostate cancer; miR-210; miR-221