Abstract 4046: Androgen-mediated phenotypic change in prostate carcinoma cells and the microRNA-ome

Abstract

Abstract Activation of the androgen receptor (AR) results in phenotypic change in androgen-responsive cells; for example, in the human prostate carcinoma cell line (LNCaP) androgens mediate cell proliferation. Factors controlling the range of phenotypic responses mediated by androgens are only partially understood, but include both transcriptional and post-transcriptional mechanisms. One such mechanism that appears to offer wide ranging, yet highly selective control, is the expression of the miRNA-ome. In the present study, we assessed the influence of endocrine-active compounds that act via the AR pathway on the microRNA (miRNA) profile. As negative regulators of gene expression, miRNA are short non-coding RNA that are able to suppress translation or induce degradation of their target mRNA transcripts (post-transcriptional) leading to decreased protein expression. The effect of exposure of LNCaP cells to the AR agonists mibolerone and dihydrotestosterone, and the antagonist bicalutamide, was determined at various time points up to 120 hours. Phenotypic response to exposure was assessed as an alteration of proliferative ability, expression of prostate-specific antigen (PSA) and alteration of the miRNA-ome. As expected, each of the agonists significantly induced proliferation, compared to vehicle control, and the antagonist decreased proliferation. Concurrent with changes in proliferation, were an up-regulation of PSA secretion for mibolerone and DHT. The temporal effects of exposure to androgenic compounds on the expression profile of 850 miRNAs was assessed using Agilent's miRNA microarray version 3. The ability of androgens to alter the miRNA-ome was confirmed and found to be temporally-dependent. Bioinformatic analysis of the phenotypic changes induced by the androgens is reflected in the changes in the miRNA-ome. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4046.