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

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...

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Autores principales: Lin, Dong, Dong, Xin, Wang, Kendric, Wyatt, Alexander W., Crea, Francesco, Xue, Hui, Wang, Yuwei, Wu, Rebecca, Bell, Robert H., Haegert, Anne, Brahmbhatt, Sonal, Hurtado-Coll, Antonio, Gout, Peter W., Fazli, Ladan, Gleave, Martin E., Collins, Colin C., Wang, Yuzhuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359333/
https://www.ncbi.nlm.nih.gov/pubmed/25544761
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author Lin, Dong
Dong, Xin
Wang, Kendric
Wyatt, Alexander W.
Crea, Francesco
Xue, Hui
Wang, Yuwei
Wu, Rebecca
Bell, Robert H.
Haegert, Anne
Brahmbhatt, Sonal
Hurtado-Coll, Antonio
Gout, Peter W.
Fazli, Ladan
Gleave, Martin E.
Collins, Colin C.
Wang, Yuzhuo
author_facet Lin, Dong
Dong, Xin
Wang, Kendric
Wyatt, Alexander W.
Crea, Francesco
Xue, Hui
Wang, Yuwei
Wu, Rebecca
Bell, Robert H.
Haegert, Anne
Brahmbhatt, Sonal
Hurtado-Coll, Antonio
Gout, Peter W.
Fazli, Ladan
Gleave, Martin E.
Collins, Colin C.
Wang, Yuzhuo
author_sort Lin, Dong
collection PubMed
description 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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spelling pubmed-43593332015-03-26 Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer Lin, Dong Dong, Xin Wang, Kendric Wyatt, Alexander W. Crea, Francesco Xue, Hui Wang, Yuwei Wu, Rebecca Bell, Robert H. Haegert, Anne Brahmbhatt, Sonal Hurtado-Coll, Antonio Gout, Peter W. Fazli, Ladan Gleave, Martin E. Collins, Colin C. Wang, Yuzhuo Oncotarget Research Paper 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. Impact Journals LLC 2014-12-11 /pmc/articles/PMC4359333/ /pubmed/25544761 Text en Copyright: © 2015 Lin et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
spellingShingle Research Paper
Lin, Dong
Dong, Xin
Wang, Kendric
Wyatt, Alexander W.
Crea, Francesco
Xue, Hui
Wang, Yuwei
Wu, Rebecca
Bell, Robert H.
Haegert, Anne
Brahmbhatt, Sonal
Hurtado-Coll, Antonio
Gout, Peter W.
Fazli, Ladan
Gleave, Martin E.
Collins, Colin C.
Wang, Yuzhuo
Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer
title Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer
title_full Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer
title_fullStr Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer
title_full_unstemmed Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer
title_short Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer
title_sort identification of dek as a potential therapeutic target for neuroendocrine prostate cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359333/
https://www.ncbi.nlm.nih.gov/pubmed/25544761
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