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Androgen receptor is a back-door inhibitor of Androgen Receptor is a Backdoor Inhibitor of Wildtype and Mutant Estrogen Receptors in Refractory Hormone Receptor-Positive Breast Cancers

ABSTRACT: HCI-13 patient-derived xenograft was treated with vehicle or a tissue-selective androgen receptor modulator (SARM), enobosarm. RNA was extracted from the tumors and microarray was performed. Objective: The objective of the study is to determine the effect of an androgen receptor (AR) agonist or a selective AR modulator (SARM) on hormone receptor-positive breast cancer growth in preclinical models and to determine the underlying mechanism of action.

ORGANISM(S): Homo sapiens

PROVIDER: GSE126318 | GEO | 2019/07/31

REPOSITORIES: GEO

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Androgen receptor agonists increase muscle mass and function in preclinical models of DMD

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

Project 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. Keywords: Comparative gene expression analysis, cell culture, prostate carcinoma, androgen receptor, selective modulators of androgen receptor, SARM

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Androgen receptor RIME using LNCaP cells

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2018-10-26 | PXD005575 | Pride

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