Abstract 2117: Constitutively active androgen receptor variants upregulate expression of mesenchymal markers in prostate cancer cells

Androgen receptor (AR) signaling pathway remains the main target of novel therapeutics for castration-resistant prostate cancer (CRPC). However, constitutively active AR variants lacking the carboxy-terminal region in CRPC lead to therapy inefficacy. Moreover, recent studies suggest that AR variants are expressed in primary prostate tumors and may contribute to tumor progression. The aim of this study was to investigate the impact of AR variants on tumor progression. N-cadherin expression was analyzed in LNCaP cells overexpressing the wild type AR or a constitutively active AR variant by qRT-PCR, Western blot and immunofluorescence. We showed here for the first time that N-cadherin expression was increased in the presence of constitutively active AR variants. Moreover, this increased expression of N-cadherin in LNCaP overexpressing AR variants was negatively regulated by androgens. Although N-cadherin expression is often associated with a downregulation of E-cadherin, this phenomenon was not observed in our model. Nevertheless, in addition to the increased expression of N-cadherin, an upregulation of other mesenchymal markers expression such as Vimentin, SNAIL and ZEB1 was observed in the presence of constitutively active AR variants. In conclusion, our findings highlight novel consequences of constitutively active AR variants on the regulation of mesenchymal markers in prostate cancer. Citation Format: Felicie COTTARD, Irene ASMANE, Eva ERDMANN, Jean-Pierre BERGERAT, Jean-Emmanuel KURTZ, Jocelyn CERALINE. Constitutively active androgen receptor variants upregulate expression of mesenchymal markers in prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2117. doi:10.1158/1538-7445.AM2014-2117