Inhibition of protein kinase CK2 leads to a modulation of androgen receptor dependent transcription in prostate cancer cells.
BACKGROUND
The androgen receptor (AR) mediates the biological responses of androgens in the prostate gland. In prostate cancer, this pathway is often deregulated and causes an uncontrolled proliferation.


METHODS
The current study focuses on the effects of an inhibition of protein kinase CK2 on the AR-mediated transcription in LNCaP prostate cancer cells. We used chemical inhibitors of CK2 as well as dominant-negative kinase mutants to downregulate the CK2 activity. We determined the effects of the inhibition by Western blot analysis of endogenous target genes of the AR as well as by reporter assays.


RESULTS
We found that inhibition of CK2 led to a downregulation of the AR-dependent transcription. Moreover, the amount of the AR protein decreased significantly.


CONCLUSIONS
According to the fact that AR pathways are involved in the development and progression of prostate cancer, the ability to modulate AR function should provide an alternative basis for the development of new cancer therapies.
Götz
Claudia
C
Universität des Saarlandes, Medizinische Biochemie und Molekularbiologie, Homburg, Germany. bccgoe@uniklinik-saarland.de
Bachmann
Christa
C
Montenarh
Mathias
M
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D001562:Benzimidazoles / Q000494:pharmacology; D015153:Blotting, Western; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004642:Emodin / Q000494:pharmacology; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
C492322:2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole; D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D011944:Receptors, Androgen; D047390:Casein Kinase II; D017430:Prostate-Specific Antigen; D004642:Emodin