Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer
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Dong Lin1, Xin Dong2, Kendric Wang1, Alexander W. Wyatt1, Francesco Crea1,2, Hui Xue2, Yuwei Wang2, Rebecca Wu2, Robert H. Bell1, Anne Haegert1, Sonal Brahmbhatt1, Antonio Hurtado-Coll1, Peter W. Gout2, Ladan Fazli1, Martin E. Gleave1, Colin C. Collins1, Yuzhuo Wang1,2
1Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada
2Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada
Yuzhuo Wang, e-mail: [email protected]
Keywords: neuroendocrine prostate cancer, patient-derived xenograft model, DEK, biomarker
Received: September 11, 2014 Accepted: November 24, 2014 Published: December 11, 2014
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.
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