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Hormonal regulation of beta(2)-adrenergic receptor level in prostate cancer

Ramberg, Hakon; Eide, Turid; Krobert, Kurt Allen; Levy, Finn Olav; Dizeyi, Nishtman LU ; Bjartell, Anders LU ; Abrahamsson, Per-Anders LU and Tasken, Kristin Austlid (2008) In The Prostate 68(10). p.1133-1142
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
triiodothyronine, bicalutamide, LNCaP cells
in
The Prostate
volume
68
issue
10
pages
1133 - 1142
publisher
John Wiley & Sons
external identifiers
  • wos:000257156400011
  • scopus:45749085708
ISSN
0270-4137
DOI
10.1002/pros.20778
language
English
LU publication?
yes
id
212149a5-7977-4914-a83c-b39844c9b9a4 (old id 1187319)
date added to LUP
2008-09-05 11:31:24
date last changed
2017-03-12 03:33:40
@article{212149a5-7977-4914-a83c-b39844c9b9a4,
  abstract     = {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.},
  author       = {Ramberg, Hakon and Eide, Turid and Krobert, Kurt Allen and Levy, Finn Olav and Dizeyi, Nishtman and Bjartell, Anders and Abrahamsson, Per-Anders and Tasken, Kristin Austlid},
  issn         = {0270-4137},
  keyword      = {triiodothyronine,bicalutamide,LNCaP cells},
  language     = {eng},
  number       = {10},
  pages        = {1133--1142},
  publisher    = {John Wiley & Sons},
  series       = {The Prostate},
  title        = {Hormonal regulation of beta(2)-adrenergic receptor level in prostate cancer},
  url          = {http://dx.doi.org/10.1002/pros.20778},
  volume       = {68},
  year         = {2008},
}