Data from Alterations Associated with Androgen Receptor Gene Activation in Salivary Duct Carcinoma of Both Sexes: Potential Therapeutic Ramifications

Abstract

<div>Abstract<p><b>Purpose:</b> To investigate the molecular events associated with the activation of androgen receptor (AR) as a potential therapeutic target in patients with salivary duct carcinoma (SDC).</p><p><b>Experimental Design:</b> Comprehensive molecular and expression analysis of the AR gene in 35 tumor specimens (20 males and 15 females) and cell lines derived from SDC using Western blotting and RT-PCR, FISH analysis, and DNA sequencing was conducted. <i>In vitro</i> and <i>in vivo</i> animal studies were also performed.</p><p><b>Results:</b> AR expression was detected in 70% of the tumors and was mainly nuclear and homogenous in both male and female SDCs, although variable cytoplasmic and/or nuclear localization was also found. We report the identification of ligand-independent <i>AR</i> splice variants, mutations, and extra <i>AR</i> gene copy in primary untreated SDC tumors. In contrast to prostate cancer, no <i>AR</i> gene amplification was observed. <i>In vitro</i> knockdown of AR in a female derived SDC cell line revealed marked growth inhibition in culture and <i>in vivo</i> androgen-independent tumor growth.</p><p><b>Conclusions:</b> Our study provides new detailed information on the molecular and structural alterations associated with <i>AR</i> gene activation in SDC and sheds more light on the putative functional role of AR in SDC cells. On the basis of these data, we propose that patients with SDC (male and female) can be stratified for hormone-based therapy in future clinical trials. <i>Clin Cancer Res; 20(24); 6570–81. ©2014 AACR</i>.</p></div>