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Accession IconGSE4636

Differential redulation of gene expression by an RTI SARM and canonical agonist of androgen receptor

Organism Icon Homo sapiens
Sample Icon 36 Downloadable Samples
Technology Badge Icon Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133B Array (hgu133b)

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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.
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