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鉴定DEK作为神经内分泌前列腺癌的潜在治疗靶点。

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

作者信息

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

机构信息

Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.

Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.

出版信息

Oncotarget. 2015 Jan 30;6(3):1806-20. doi: 10.18632/oncotarget.2809.

DOI:10.18632/oncotarget.2809
PMID:25544761
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4359333/
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.

摘要

神经内分泌前列腺癌（NEPC）是前列腺癌的一种侵袭性亚型，对激素治疗无反应。由于缺乏临床相关的体内模型，NEPC的研究受到了阻碍。最近，我们开发了一种首创的患者组织来源的异种移植模型，用于前列腺腺癌的完全神经内分泌转分化。通过比较可移植腺癌系（LTL331）及其NEPC亚系（LTL331R）的基因表达谱，我们确定DEK为NEPC的潜在生物标志物和治疗靶点。在本研究中，在所有NEPC异种移植模型和临床NEPC病例中均观察到DEK蛋白表达升高，而其良性对应物（0%）、激素初治前列腺癌（2.45%）和去势抵抗性前列腺癌（29.55%）则未观察到。发现DEK表达升高是一种独立的临床风险因素，与激素初治前列腺癌患者较短的无病生存期相关。在PC-3细胞中沉默DEK导致细胞增殖、细胞迁移和侵袭显著减少。结果表明，DEK在前列腺癌尤其是向NEPC的进展中起重要作用，并为辅助前列腺癌风险分层提供了潜在的生物标志物，以及为NEPC治疗提供了新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded3/4359333/c5e959391dd3/oncotarget-06-1806-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded3/4359333/122008283cef/oncotarget-06-1806-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded3/4359333/60ca3d4db522/oncotarget-06-1806-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded3/4359333/8df069ac4e2c/oncotarget-06-1806-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded3/4359333/c5e959391dd3/oncotarget-06-1806-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded3/4359333/122008283cef/oncotarget-06-1806-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded3/4359333/60ca3d4db522/oncotarget-06-1806-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded3/4359333/8df069ac4e2c/oncotarget-06-1806-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded3/4359333/c5e959391dd3/oncotarget-06-1806-g004.jpg

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