Investigation Title Transcription profiling of human LNCaP cells treated with DHT, RTI-6413-018 or vehicle to identify useful Selective Androgen Receptor Modulators (SARMs) Comment[Submitted Name] Differential redulation of gene expression by an RTI SARM and canonical agonist of androgen receptor Experimental Design time_series_design cell_type_comparison_design compound_treatment_design co-expression_design transcription profiling by array Experimental Design Term Source REF mo mo mo mo EFO Comment[ArrayExpressReleaseDate] 2007-12-19 Comment[SecondaryAccession] GSE4636 Comment[AEMIAMESCORE] 4 Comment[SecondaryAccession] GDS2058 Comment[SecondaryAccession] GDS2057 Comment[ArrayExpressAccession] E-GEOD-4636 Comment[MAGETAB TimeStamp_Version] 2011-06-30 21:26:56 Last Changed Rev: 14857 Experimental Factor Name Time Dose Compound Experimental Factor Type time dose compound Experimental Factor Term Source REF Person Last Name Kazmin Person First Name Dmitri Person Mid Initials A. Person Email kazmi002@mc.duke.edu Person Phone Person Fax Person Address McDonnell,Pharmacology and Cancer Biology,Duke University Medical Center,C264 LSRC, Research Dr,Durham,27710,USA Person Affiliation Duke University Medical Center Person Roles submitter Person Roles Term Source REF Quality Control Type Quality Control Term Source REF Replicate Type Replicate Term Source REF Normalization Type Normalization Term Source REF Date of Experiment Public Release Date 2007-12-19 PubMed ID 16574741 Publication DOI 16574741 Publication Author List Dmitri Kazmin,Tatiana Prytkova,C Edgar Cook,Russell Wolfinger,Tzu-Ming Chu,David Beratan,J D Norris,Ching-yi Chang,Donald P McDonnell Publication Title Linking ligand-induced alterations in androgen receptor structure to differential gene expression: a first step in the rational design of selective androgen receptor modulators. Publication Status journal_article Publication Status Term Source REF The MGED Ontology Experiment Description We have previously identified a family of novel androgen receptor (AR) ligands that, upon binding, enable AR to adopt structures distinct from that observed in the presence of canonical agonists. In this report, we describe the use of these compounds to establish a relationship between AR structure and biological activity with a view to defining a rational approach with which to identify useful Selective Androgen Receptor Modulators (SARMs). As one of the approaches, we used a DNA microarray analysis to demonstrate that differently conformed receptors facilitate distinct patterns of gene expression in LNCaP cells. Interestingly, we observed a complete overlap in the identity of genes expressed following treatment with mechanistically distinct AR ligands. However, it was differences in the kinetics of gene regulation that distinguished these compounds. Follow-up studies, in cell-based assays of AR action, confirmed the importance of these alterations in gene expression. Together these studies demonstrate an important link between AR structure, gene expression and biological outcome. In this experiment LNCaP cells (400,000 per 75 cm2 flask) were first incubated in DMEM/8% charcoal-stripped serum to reduce the background hormone exposure, and then were treated with Vehicle (ethanol), DHT (10 nM) or RTI-6413-018 (100 nM). Treatment was done for 6 and 24 hrs. At the end of treatment, cells were collected by trypsization and immediately frozen in liquid nitrogen. Isolation of mRNA was performed using Qiagen Oligotex midi kit. cRNA synthesis, labeling and hybridization were performed by Expression Analysis Institute, Durham, NC. Samples were hybridized to Affymetrix HG.U133 A and B chips. Experiment was repeated three times. Protocol Name Protocol Type Protocol Description Protocol Parameters Protocol Hardware Protocol Software Protocol Contact Protocol Term Source REF SDRF File E-GEOD-4636.sdrf.txt Term Source Name mo NCI_thesaurus The MGED Ontology ArrayExpress mo EFO The MGED Ontology Term Source File http://mged.sourceforge.net/ontologies/MGEDontology.php ncithesaurus.obo.alt http://mged.sourceforge.net/ontologies/MGEDontology.php http://www.ebi.ac.uk/arrayexpress http://mged.sourceforge.net/ontologies/MGEDontology.php http://www.ebi.ac.uk/efo/ http://mged.sourceforge.net/ontologies/MGEDontology.php Term Source Version