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

Dong Lin1, Xin Dong2, Kendric Wang1

  • 1Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.

Oncotarget
|December 30, 2014
PubMed

Insights

DEK protein shows elevated expression in neuroendocrine prostate cancer (NEPC), unlike other prostate cancer types. This finding suggests DEK as a potential biomarker for risk stratification and a therapeutic target for NEPC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Neuroendocrine prostate cancer (NEPC) is an aggressive subtype resistant to standard hormone therapy.
  • Lack of effective in vivo models has hindered NEPC research.
  • A novel patient-derived xenograft model of neuroendocrine prostate cancer (NEPC) was recently developed.

Purpose of the Study:

  • To investigate the role of DEK in prostate cancer progression, particularly to NEPC.
  • To evaluate DEK as a potential biomarker for NEPC risk stratification.
  • To explore DEK as a therapeutic target for NEPC.

Main Methods:

  • Gene expression profiling of prostate adenocarcinoma and NEPC subline xenografts.
  • Analysis of DEK protein expression in NEPC xenografts and clinical samples.
  • Assessment of DEK's association with clinical risk factors and patient survival.
  • In vitro studies involving DEK silencing in prostate cancer cells (PC-3).

Main Results:

  • DEK protein expression is significantly elevated in all NEPC models and clinical cases, but not in benign or early-stage prostate cancers.
  • Elevated DEK expression is an independent risk factor for shorter disease-free survival in prostate cancer patients.
  • DEK silencing in PC-3 cells reduced cell proliferation, migration, and invasion.

Conclusions:

  • DEK plays a critical role in prostate cancer progression towards NEPC.
  • DEK serves as a potential biomarker for prostate cancer risk stratification.
  • DEK represents a promising therapeutic target for neuroendocrine prostate cancer.

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