Hormonal regulation of beta(2)-adrenergic receptor level in prostate cancer
(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:
https://lup.lub.lu.se/record/1187319
- author
- Ramberg, Hakon ; Eide, Turid ; Krobert, Kurt Allen ; Levy, Finn Olav ; Dizeyi, Nishtman LU ; Bjartell, Anders LU ; Abrahamsson, Per-Anders LU and Tasken, Kristin Austlid
- organization
- publishing date
- 2008
- 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 Inc.
- 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
- 2016-04-01 12:13:46
- date last changed
- 2022-03-13 07:06:54
@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}}, keywords = {{triiodothyronine; bicalutamide; LNCaP cells}}, language = {{eng}}, number = {{10}}, pages = {{1133--1142}}, publisher = {{John Wiley & Sons Inc.}}, series = {{The Prostate}}, title = {{Hormonal regulation of beta(2)-adrenergic receptor level in prostate cancer}}, url = {{http://dx.doi.org/10.1002/pros.20778}}, doi = {{10.1002/pros.20778}}, volume = {{68}}, year = {{2008}}, }