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A Latil

A-H Ma

Alfonso Urbanucci

B Comuzzi

C Huggins

CA Heinlein

CD Chen

CI Truica

CJ Burd

D Romagnolo

DJ Mulholland

DK Lee

DM Lonard

EA Mostaghel

F Yang

Hanna E Suikki

I Irminger-Finger

IM Thompson

JE Pawloski

JJ Park

JM Gudas

JT Isaacs

K Haapala

Kati K Waltering

KJ Lauritsen

L Jia

L Xia

LD Snider

LN Song

M Rahman

ME Taplin

Merja A Helenius

MJ Linja

MJ Wallén

MR Cooperberg

N Fujimoto

N Rahman

P Boyle

PJ Morin

R Chmelar

RF Gittes

S Perner

SA Tomlins

SL Anzick

SP Balk

T Hara

T Visakorpi

Tapio Visakorpi

Z Culig

English

PubMed

Springer - Publisher Connector

Androgen regulation of the androgen receptor coregulators

Crossref

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, β-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 β-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 β-catenin, cyclinD1 and gelsolin.

Conclusion

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.BioMed Central Open acces

Urbanucci, Alfonso

Waltering, Kati K

Suikki, Hanna E

Helenius, Merja A

Visakorpi, Tapio

TamPub Julkaisuarkisto - TamPub Institutional Repository

Trepo - Institutional Repository of Tampere University

Abstract 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, β-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 β-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 β-catenin, cyclinD1 and gelsolin. Conclusion 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.</p

Helenius Merja A

Suikki Hanna E

Waltering Kati K

Urbanucci Alfonso

Visakorpi Tapio

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Androgen regulation of the androgen receptor coregulators

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