Androgen regulation of the androgen receptor coregulators.
BACKGROUND
The critical role of the androgen receptor (AR) in the development of prostate cancer is well recognized. The transcriptional activity of AR is partly regulated by coregulatory proteins. It has been suggested that these coregulators could also be important in the progression of prostate cancer. The aim of this study was to identify coregulators whose expression is regulated by either the androgens and/or by the expression level of AR.


METHODS
We used empty vector and AR cDNA-transfected LNCaP cells (LNCaP-pcDNA3.1, and LNCaP-ARhi, respectively), and grew them for 4 and 24 hours in the presence of dihydrotestosterone (DHT) at various concentrations. The expression of 25 AR coregulators (SRC1, TIF2, PIAS1, PIASx, ARIP4, BRCA1, beta-catenin, AIB3, AIB1, CBP, STAT1, NCoR1, AES, cyclin D1, p300, ARA24, LSD1, BAG1L, gelsolin, prohibitin, JMJD2C, JMJD1A, MAK, PAK6 and MAGE11) was then measured by using real-time quantitative RT-PCR (Q-RT-PCR).


RESULTS
Five of the coregulators (AIB1, CBP, MAK, BRCA1 and beta-catenin) showed more than 2-fold induction and 5 others (cyclin D1, gelsolin, prohibitin, JMJD1A, and JMJD2C) less than 2-fold induction. Overexpression of AR did not affect the expression of the coregulators alone. However, overexpression of AR enhanced the DHT-stimulated expression of MAK, BRCA1, AIB1 and CBP and reduced the level of expression of beta-catenin, cyclinD1 and gelsolin.


CONCLUSIONS
In conclusion, we identified 5 coactivators whose expression was induced by androgens suggesting that they could potentiate AR signaling. Overexpression of AR seems to sensitize cells for low levels of androgens.
Urbanucci
Alfonso
A
Institute of Medical Technology, University of Tampere and Tampere University Hospital, FI-33014 University of Tampere, Tampere, Finland. alfonso.urbanucci@uta.fi
Waltering
Kati K
KK
Suikki
Hanna E
HE
Helenius
Merja A
MA
Visakorpi
Tapio
T
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D013196:Dihydrotestosterone / Q000494:pharmacology; D018450:Disease Progression; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors
D000728:Androgens; D011944:Receptors, Androgen; D013196:Dihydrotestosterone