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Activation of the androgen receptor by polypeptide growth factors and cellular regulators

Z Culig1, A Hobisch, M V Cronauer

  • 1Department of Urology, University of Innsbruck, Austria.

World Journal of Urology
|January 1, 1995
PubMed

Insights

Growth factors and signaling molecules can activate hormone receptors like the androgen receptor (AR) without hormones. This influences prostate cancer cell growth, even in low-androgen conditions.

Area of Science:

  • Molecular Endocrinology
  • Cell Signaling
  • Cancer Biology

Background:

  • Hormone receptors (ER, PR, GR) are activated by growth factors, cAMP, and neurotransmitters.
  • Emerging evidence suggests similar cross-talk with the androgen receptor (AR).

Purpose of the Study:

  • To investigate the role of growth factors and signaling molecules in activating the androgen receptor (AR).
  • To explore the impact of AR activation on prostate cancer cell growth in androgen-depleted environments.

Main Methods:

  • Reporter-gene assays in DU-145 and CV-1 cells to measure AR-mediated transcription.
  • Prostate-specific antigen (PSA) level measurement in LNCaP cells.
  • Assessing the effect of retinoic acid on androgen-stimulated activity.

Main Results:

  • Polypeptide growth factors (IGF-I, KGF, EGF) stimulated AR-mediated transcription without androgens.
  • IGF-I increased PSA levels in LNCaP cells.
  • cAMP potentiated testosterone's effect on AR activity.
  • Retinoic acid inhibited androgen-stimulated activity.

Conclusions:

  • Signaling pathways involving the AR can be activated by growth factors and second messengers independently of androgens.
  • AR activation in an androgen-depleted environment may influence prostatic carcinoma cell growth.

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