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 β₂‐adrenergic receptor (β₂‐AR) is a well‐known activator of the androgen receptor.

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.

Here, we show that β₂‐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 β‐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 β₂‐AR and the effect of T3 was inhibited by bicalutamide. Immunohistochemical staining of human prostate specimens showed high expression of β₂‐AR in glandular, epithelial cells and increased expression in malignant cells compared to benign hyperplasia and normal tissue. Interestingly, β₂‐AR mRNA was strongly down‐regulated by androgen ablation therapy of prostate cancer patients.

The level of β₂‐AR was increased by T3 in prostatic adenocarcinoma cells and reduced in prostate cancer patients who had received androgen ablation therapy for 3 months. Prostate 68:1133–1142, 2008. © 2008 Wiley‐Liss, Inc.