TY  - JOUR
A1  - Urbanucci, Alfonso
A1  - Barfeld, Stefan J.
A1  - Kytölä, Ville
A1  - Itkonen, Harri M.
A1  - Coleman, Ilsa M.
A1  - Vodák, Daniel
A1  - Sjöblom, Liisa
A1  - Sheng, Xia
A1  - Tolonen, Teemu
A1  - Minner, Sarah
A1  - Burdelski, Christoph
A1  - Kivinummi, Kati K.
A1  - Kohvakka, Annika
A1  - Kregel, Steven
A1  - Takhar, Mandeep
A1  - Alshalalfa, Mohammed
A1  - Davicioni, Elai
A1  - Erho, Nicholas
A1  - Lloyd, Paul
A1  - Karnes, R. Jeffrey
A1  - Ross, Ashley E.
A1  - Schaeffer, Edward M.
A1  - Vander Griend, Donald J.
A1  - Knapp, Stefan
A1  - Corey, Eva
A1  - Feng, Felix Y.
A1  - Nelson, Peter S.
A1  - Saatcioglu, Fahri
A1  - Knudsen, Karen E.
A1  - Tammela, Teuvo L. J.
A1  - Sauter, Guido
A1  - Schlomm, Thorsten
A1  - Nykter, Matti
A1  - Visakorpi, Tapio
A1  - Mills, Ian G.
T1  - Androgen receptor deregulation drives bromodomain-mediated chromatin alterations in prostate cancer
T2  - Cell reports
N2  - Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene stratification signature (BROMO-10) for bromodomain response and PC prognostication, to inform current and future trials with drugs targeting these processes. Our findings provide a compelling rational for combination therapy targeting bromodomains in selected patients in which BRD-mediated TF binding is enhanced or modified as cancer progresses.
KW  - ATAD2
KW  - BRD2
KW  - BRD4
KW  - BROMO-10
KW  - androgen receptor
KW  - bromodomain inhibitor
KW  - castration-resistant prostate cancer
KW  - chromatin
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45889
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-458899
SN  - 2211-1247
N1  - This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
VL  - 19
IS  - 10
SP  - 2045
EP  - 2059
PB  - Elsevier
CY  - [New York, NY]
ER  -