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Updated: May 31, 2026

Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses
08:36

Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses

Published on: October 24, 2019

Androgen receptor coregulators NOCR1, TIF2, and ARA70 may account for the hydroxyflutamide insensitivity of prostate

Y Wang1, J-Q Li, C Shao

  • 1Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi, China. dryongwangfmmu@yahoo.com.cn

Irish Journal of Medical Science
|July 13, 2011
PubMed
Abstract

Insights

Prostate cancer cells can become resistant to androgen ablation therapy. This study found that changes in androgen receptor (AR) coregulator genes, not AR levels, drive this antiandrogen insensitivity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer can evolve from androgen-dependent to androgen-independent states under therapy.
  • The molecular mechanisms driving this therapeutic resistance remain largely unknown.

Purpose of the Study:

  • To investigate changes in androgen receptor (AR)-related gene expression during the transition to androgen independence in prostate cancer.
  • To identify key molecular players involved in the development of antiandrogen insensitivity.

Main Methods:

  • Developed a novel cell model (LNCaP-flu) of flutamide-insensitive prostate cancer by continuous hydroxyflutamide treatment.
  • Analyzed differential gene expression between LNCaP-flu and parental LNCaP cells using gene chips and RT-PCR.

Main Results:

  • Over 2,428 genes showed differential expression between the cell lines.
  • NCOR1, TIF2 (NCOA2), and ARA70 (NCOA4) were identified as key AR-related genes involved in the transition.
  • Expression of the androgen receptor (AR) and prostate-specific antigen (PSA) remained unchanged.

Conclusions:

  • Androgen receptors (ARs) and their associated coregulators are crucial in the development of flutamide insensitivity.
  • Altered expression of AR coregulators, rather than AR levels, is a critical factor in prostate cancer's antiandrogen insensitivity.

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