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Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer.
- Source :
-
Oncotarget [Oncotarget] 2015 Jan 30; Vol. 6 (3), pp. 1806-20. - Publication Year :
- 2015
-
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.
- Subjects :
- Adult
Aged
Carcinoma, Neuroendocrine pathology
Chromosomal Proteins, Non-Histone genetics
Disease-Free Survival
Humans
Male
Middle Aged
Molecular Targeted Therapy
Oncogene Proteins genetics
Poly-ADP-Ribose Binding Proteins
Prostatic Neoplasms pathology
Prostatic Neoplasms, Castration-Resistant pathology
Xenograft Model Antitumor Assays
Carcinoma, Neuroendocrine metabolism
Chromosomal Proteins, Non-Histone biosynthesis
Oncogene Proteins biosynthesis
Prostatic Neoplasms metabolism
Prostatic Neoplasms, Castration-Resistant metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 25544761
- Full Text :
- https://doi.org/10.18632/oncotarget.2809