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GnRH receptor expression in human prostate cancer cells is affected by hormones and growth factors

Cristiana Angelucci1, Gina Lama, Fortunata Iacopino

  • 1Institute of Histology and Embryology, Catholic University of the Sacred Heart, Largo Francesco Vito 1, 00168, Rome, Italy. cristiana.angelucci@rm.unicatt.it

Endocrine
|April 29, 2009
PubMed

Insights

Leuprorelin acetate (LA) upregulates its own GnRH receptors in prostate cancer cells post-transcriptionally. This finding suggests GnRH receptors are a potential therapeutic target, especially in hormone-refractory prostate cancer.

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • GnRH receptors (GnRH-R) are present in various cancers, including prostate cancer (PCa).
  • GnRH analogs exert direct antitumor effects via GnRH-R, but drug-induced modulation of these receptors is poorly understood.
  • Understanding GnRH-R regulation is crucial for optimizing GnRH analog therapy and developing new treatments for PCa.

Purpose of the Study:

  • To investigate the effects of various agents on GnRH-R expression in androgen-sensitive (LNCaP) and androgen-insensitive (PC-3) PCa cells.
  • To determine if GnRH analogs, androgens, or growth factors modulate GnRH-R levels.
  • To explore the therapeutic potential of targeting GnRH-R in PCa.

Main Methods:

  • Prostate cancer cell lines (LNCaP and PC-3) were treated with GnRH agonist (Leuprorelin acetate, LA), Dihydrotestosterone (DHT), Cyproterone acetate (CA), and Epidermal growth factor (EGF).
  • Gene expression was analyzed using RT-PCR for GnRH-R mRNA levels.
  • Protein expression of membrane GnRH-R was assessed via immunoblotting after 4, 6, and 12 days of treatment.

Main Results:

  • RT-PCR showed no significant changes in GnRH-R mRNA levels across all treatments.
  • Immunoblotting revealed that LA significantly upregulated membrane GnRH-R in both LNCaP and PC-3 cells (up to 92%).
  • DHT and CA also increased GnRH-R in LNCaP cells, while EGF upregulated GnRH-R in PC-3 cells, with prolonged treatment yielding higher increases (up to 142%). LA treatment counteracted the receptor upregulation by DHT and EGF.

Conclusions:

  • Leuprorelin acetate post-transcriptionally upregulates its own membrane GnRH receptor in both androgen-sensitive and -insensitive PCa cells.
  • This upregulation counteracts the effects of DHT and EGF on GnRH-R levels.
  • The findings highlight GnRH-R as a potential therapeutic target, particularly in hormone-refractory prostate cancer, and have implications for GnRH analog therapy strategies.

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