Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer

Abstract

// Dong Lin 1 , Xin Dong 2 , Kendric Wang 1 , Alexander W. Wyatt 1 , Francesco Crea 1, 2 , Hui Xue 2 , Yuwei Wang 2 , Rebecca Wu 2 , Robert H. Bell 1 , Anne Haegert 1 , Sonal Brahmbhatt 1 , Antonio Hurtado-Coll 1 , Peter W. Gout 2 , Ladan Fazli 1 , Martin E. Gleave 1 , Colin C. Collins 1 , Yuzhuo Wang 1, 2 1 Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada 2 Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada Correspondence to: Yuzhuo Wang, e-mail: ywang@bccrc.ca Keywords: neuroendocrine prostate cancer, patient-derived xenograft model, DEK, biomarker Received: September 11, 2014      Accepted: November 24, 2014      Published: December 11, 2014 ABSTRACT Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer which does not respond to hormone therapy. Research of NEPC has been hampered by a lack of clinically relevant in vivo models. Recently, we developed a first-in-field patient tissue-derived xenograft model of complete neuroendocrine transdifferentiation of prostate adenocarcinoma. By comparing gene expression profiles of a transplantable adenocarcinoma line (LTL331) and its NEPC subline (LTL331R), we identified DEK as a potential biomarker and therapeutic target for NEPC. In the present study, elevated DEK protein expression was observed in all NEPC xenograft models and clinical NEPC cases, as opposed to their benign counterparts (0%), hormonal naïve prostate cancer (2.45%) and castration-resistant prostate cancer (29.55%). Elevated DEK expression was found to be an independent clinical risk factor, associated with shorter disease-free survival of hormonal naïve prostate cancer patients. DEK silencing in PC-3 cells led to a marked reduction in cell proliferation, cell migration and invasion. The results suggest that DEK plays an important role in the progression of prostate cancer, especially to NEPC, and provides a potential biomarker to aid risk stratification of prostate cancer and a novel target for therapy of NEPC.