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Androgen and anti-androgen treatment modulates androgen receptor activity and DJ-1 stability

Tiina Pitkänen-Arsiola1, J Erin Tillman, Guangyu Gu

  • 1Institute of Applied Biotechnology, University of Kuopio, Kuopio, Finland.

The Prostate
|May 3, 2006
PubMed
Abstract

Insights

Researchers discovered DJ-1 stabilizes the androgen receptor (AR), potentially driving hormone-refractory prostate cancer (PCa) progression. This finding sheds light on how prostate cancer becomes resistant to treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Mechanisms of prostate cancer (PCa) progression from hormone-responsive to hormone-refractory states are not fully understood.
  • Hormone therapy is a primary treatment for PCa, but resistance eventually develops.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying the transition to hormone-refractory prostate cancer.
  • To identify regulators of androgen receptor (AR) activity during anti-androgen treatment.

Main Methods:

  • Primary human prostate epithelial (HPE) cells from patient specimens were used.
  • A transiently infected gene reporter (TIGR) assay assessed endogenous AR activity under androgen and anti-androgen treatment.
  • Proteomic analysis compared cells exhibiting different responses to flutamide.

Main Results:

  • Flutamide acted as an agonist in some HPE cells with wild-type AR, contrary to its expected antagonist role.
  • Proteomic analysis identified DJ-1 as a positive regulator of AR.
  • DJ-1 expression and protein stabilization increased in HPE and LNCaP cells during flutamide treatment.

Conclusions:

  • Stabilization of AR and its co-regulators, like DJ-1, in the absence of androgens may contribute to anti-androgen withdrawal syndrome.
  • This stabilization mechanism could be a key factor in the development of hormone-refractory prostate cancer.

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