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| Status |
Public on Jan 15, 2015 |
| Title |
Identification of DEK as a potential therapeutic target for Neuroendocrine prostate cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Introduction: Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer, exhibiting rapid progression and is unresponsive to hormone therapy. Reliable prognostic assays and more effective treatments are critically required. However, the research of NEPC has been hampered by a lack of clinically relevant in vivo models. Recently, we successfully developed a first-in-field patient tissue-derived xenograft model of complete neuroendocrine transdifferentiation from prostate adenocarcinoma. By comparing gene expression profiles of the parental adenocarcinoma line (LTL331) and the NEPC subline (LTL331R), we identified DEK, a gene not previously reported in prostate cancer, as a potential biomarker and target for NEPC. Methods: DEK protein expression in patient tissue-derived xenograft models and clinical samples was assessed by immunohistochemistry. The function of DEK was determined by siRNA-induced reduction of DEK expression in PC-3 cells, a cell line with NEPC characteristics, followed by functional assays and gene expression profiling analysis. Results: Elevated DEK protein expression was observed in all clinical NEPC cases, which is distinct from their benign counterparts (0%), hormonal naïve prostate cancer (2.45%) and castration resistant prostate cancer (29.55%). Increased DEK expression is an independent clinical risk factor and is associated with shorter disease free survival in hormonal naïve prostate cancer patients. Reduction of DEK expression in PC-3 cells led to a marked reduction in cell proliferation, cell migration and invasion. Conclusions: The results suggest that DEK may play an important role in the progression of prostate cancer, especially NEPC and provide a potential biomarker to aid risk stratification of prostate cancer and a novel therapeutic target for treating NEPC.
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| Overall design |
The function of DEK was determined by siRNA-induced reduction of DEK expression in PC-3 cells, a cell line with NEPC characteristics, followed by functional assays and gene expression profiling analysis.
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| Contributor(s) |
Lin D, Wyatt AW, Brahmbhatt S, Haegert A, Anderson SA |
| Citation(s) |
25544761 |
| Submission date |
Sep 08, 2014 |
| Last update date |
Oct 11, 2016 |
| Contact name |
Shawn Anderson |
| E-mail(s) |
Sanderson@prostatecentre.com
|
| Organization name |
Vancouver Prostate Centre
|
| Lab |
Laboratory for Advanced Genome Analysis
|
| Street address |
2660 Oak Street
|
| City |
Vancouver |
| State/province |
BC |
| ZIP/Postal code |
V6H3Z6 |
| Country |
Canada |
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| Platforms (1) |
| GPL14550 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA260520 |
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