Prognostic significance of the TREK-1 K2P potassium channels in prostate cancer

Oncotarget. 2015 Jul 30;6(21):18460-8. doi: 10.18632/oncotarget.3782.

Abstract

Background: TREK-1 channels belong to the two-pore domain potassium channel superfamily and play an important role in central nervous system diseases. However, few studies have examined their role in carcinogenesis.

Methods: In this study, we assessed the expression of TREK-1 in 100 prostate cancer (PCa) tissues using immunohistochemistry and further analyzed its clinicopathological significance. Next, cell proliferation and cell cycle analysis were carried out on human PCa PC-3 cell lines where TREK-1 was stably knockdown.

Results: We found that compared with normal prostate tissues, PCa tissues showed overexpressed TREK-1 levels and TREK-1 levels were positively associated with Gleason score and T staging. High level of TREK-1 expression was related to shorter castration resistance free survival (CRFS). Furthermore, knockdown of TREK-1 significantly inhibited PCa cell proliferation in vitro and in vivo, and induced a G1/S cell cycle arrest.

Conclusions: Our results suggest that TREK-1 might be a biomarker in CRFS judgment of PCa, as well as a potential therapeutic target.

Keywords: TREK-1; biochemical recurrence; cell cycle; cell proliferation; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Blotting, Western
  • Cell Cycle*
  • Cell Line, Tumor
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Immunohistochemistry / statistics & numerical data
  • Kaplan-Meier Estimate
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Potassium Channels, Tandem Pore Domain / genetics
  • Potassium Channels, Tandem Pore Domain / metabolism*
  • Prognosis
  • Proportional Hazards Models
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transplantation, Heterologous
  • Tumor Burden

Substances

  • Potassium Channels, Tandem Pore Domain
  • potassium channel protein TREK-1