Hormonal regulation of beta2-adrenergic receptor level in prostate cancer

Prostate. 2008 Jul 1;68(10):1133-42. doi: 10.1002/pros.20778.


Background: Androgen deprivation is the only effective systemic therapy available for patients with prostatic carcinoma, but is associated with a gradual transition to a hormone-refractory prostate cancer (HRCAP) in which ligand-independent activation of the androgen receptor has been implicated. The beta(2)-adrenergic receptor (beta(2)-AR) is a well-known activator of the androgen receptor.

Methods: Prostatic cell lines were analyzed using cDNA micro-array, real time RT-PCR, radioligand binding assay, cAMP measurements, transfection and thymidine incorporation assay. Clinical specimens were studied by immunohistochemistry and Affymetrix microarrays.

Results: Here, we show that beta(2)-AR was transiently down-regulated both at mRNA- and protein levels when hormone-sensitive prostate cancer cells, LNCaP, were cultured in steroid stripped medium (charcoal-stripped fetal calf serum) or when the cells were treated with the anti-androgen, bicalutamide (Casodex). The number of beta-adrenergic receptors was modestly up-regulated in androgen independent cell lines (LNCaP-C4, LNCaP-C4-2 and DU145) compared to LNCaP. Triiodothyronine (T3) increased the level of beta(2)-AR and the effect of T3 was inhibited by bicalutamide. Immunohistochemical staining of human prostate specimens showed high expression of beta(2)-AR in glandular, epithelial cells and increased expression in malignant cells compared to benign hyperplasia and normal tissue. Interestingly, beta(2)-AR mRNA was strongly down-regulated by androgen ablation therapy of prostate cancer patients.

Conclusion: The level of beta(2)-AR was increased by T3 in prostatic adenocarcinoma cells and reduced in prostate cancer patients who had received androgen ablation therapy for 3 months.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology
  • Adenocarcinoma / physiopathology*
  • Androgen Antagonists / pharmacology
  • Androgen Antagonists / therapeutic use
  • Androgens / metabolism
  • Anilides / pharmacology
  • Antineoplastic Agents / pharmacology
  • Biopsy
  • Cell Line, Tumor
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Immunohistochemistry
  • Male
  • Nitriles / pharmacology
  • Oligonucleotide Array Sequence Analysis
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / physiopathology*
  • Receptors, Adrenergic, beta-2 / genetics*
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Receptors, Androgen / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Tosyl Compounds / pharmacology
  • Triiodothyronine / pharmacology
  • Up-Regulation


  • Androgen Antagonists
  • Androgens
  • Anilides
  • Antineoplastic Agents
  • Nitriles
  • Receptors, Adrenergic, beta-2
  • Receptors, Androgen
  • Tosyl Compounds
  • Triiodothyronine
  • bicalutamide