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Updated: Jun 27, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

13.1K

Patient-derived castration-resistant prostate cancer model revealed CTBP2 upregulation mediated by OCT1 and androgen

Daisuke Obinata1,2, Kenichi Takayama3, Mitchell G Lawrence2,4,5,6

  • 1Department of Urology, Nihon University School of Medicine, 30-1, Ooyaguchikamicho, Itabashi-ku, Tokyo, 173-8610, Japan.

BMC Cancer
|May 2, 2024
PubMed
Abstract

Insights

This study reveals OCT1 and AR target gene CTBP2 promotes aggressive prostate cancer progression and immune evasion. Targeting CTBP2 may offer a new therapeutic strategy for castration-resistant prostate cancer (CRPC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Prostate cancer relies on androgen receptor (AR) signaling; androgen deprivation therapy (ADT) is effective but castration-resistant prostate cancer (CRPC) emerges.
  • Resistance to AR signaling inhibitors (ARSI) in CRPC is linked to AR alterations and epigenetic changes.

Purpose of the Study:

  • Investigate the role of OCT1 in AR-positive CRPC, focusing on a patient-derived xenograft resistant to ARSI and chemotherapy.
  • Elucidate the genome-wide network of OCT1 and AR in CRPC and identify potential therapeutic targets.

Main Methods:

  • Utilized a patient-derived xenograft (PDX) model of AR-positive CRPC.
  • Performed genome-wide chromatin immunoprecipitation followed by sequencing (ChIP-seq) for OCT1.
  • Conducted bioinformatic analyses, including Metascape and TISIDB, using public databases.

Main Results:

  • Identified distinct OCT1 binding sites in resistant CRPC cells compared to treatment-naïve cells.
  • Discovered OCT1-regulated genes are involved in cell migration and immune regulation.
  • Found C-terminal Binding Protein 2 (CTBP2), an OCT1/AR target, correlates with poor prognosis, immunosuppression, and immune evasion in CRPC.

Conclusions:

  • The study highlights the OCT1 and AR network in AR-positive CRPC.
  • CTBP2 plays a significant role in tumor progression and immune response modulation.
  • Targeting CTBP2 presents a potential therapeutic strategy for aggressive CRPC, requiring further validation.
Keywords:
Androgen receptorCTBP2OCT1Prostate cancer

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