Transcriptional Coactivators p300 and CBP Stimulate Estrogen Receptor-Beta Signaling and Regulate Cellular Events in Prostate Cancer

被引：42

作者：

Bouchal, Jan ^{[1
,2
]}

Santer, Frederic R. ^{[1
]}

Hoeschele, Philipp P. S. ^{[1
]}

Tomastikova, Eva ^{[2
]}

Neuwirt, Hannes ^{[1
,3
]}

Culig, Zoran ^{[1
]}

机构：

[1] Innsbruck Med Univ, Dept Urol, A-6020 Innsbruck, Austria

[2] Palacky Univ, Lab Mol Pathol, Inst Mol & Translat Med, Fac Med & Dent, CR-77147 Olomouc, Czech Republic

[3] Innsbruck Med Univ, Dept Internal Med 4, A-6020 Innsbruck, Austria

来源：

PROSTATE | 2011年 / 71卷 / 04期

基金：

奥地利科学基金会;

关键词：

transcriptional coactivators; prostate cancer; estrogen receptor-beta; migration; genistein; ANDROGEN RECEPTOR; TUMOR PROGRESSION; EXPRESS ESTROGEN; BINDING-PROTEIN; GENE-EXPRESSION; ER-BETA; CELLS; GROWTH; PROLIFERATION; INHIBITION;

D O I：

10.1002/pros.21257

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND. Steroid receptor coactivators p300 and CBP are highly expressed in advanced prostate cancer. They potentiate activation of androgen receptor by androgens and anti-androgens. In the present study, we have addressed the question whether these coactivators enhance activity of estrogen receptor-beta (ER-beta), which is variably expressed in prostate cancers. METHODS. Expression levels of the coactivators p300 and CBP were manipulated by plasmid or siRNA transfections and activity of ER-beta was measured by luciferase assays. Viability was measured by MTT assays and cellular migration was determined by wound-healing and Boyden chamber assays. RESULTS. High expression of ER-beta was found in PC3 cells which were used for the experiments. p300 or CBP enhanced activation of ER-beta by genistein. Antiestrogens did not acquire agonistic properties in the presence of increased concentrations of either coactivator. Inhibition of p300 or CBP decreased genistein stimulation of ER-beta. Genistein reduced migration of PC3 prostate cancer cells and down-regulation of p300 potentiated this effect. CONCLUSIONS. p300 and CBP are implicated in regulation of ER-beta activity and cellular migration in prostate cancer. These findings are important for understanding of action of ER-beta in carcinoma of the prostate. Prostate 71: 431-437, 2011. (C) 2010 Wiley-Liss, Inc.

引用

页码：431 / 437

页数：7

共 40 条

[1] Role of SRC-1 in the promotion of prostate cancer cell growth and tumor progression [J].

Agoulnik, IU ;

Vaid, A ;

Bingman, WE ;

Erdeme, H ;

Frolov, A ;

Smith, CL ;

Ayala, G ;

Ittmann, MM ;

Weigel, NL .

CANCER RESEARCH, 2005, 65 (17) :7959-7967

[2] Androgen receptor regulation by physiological concentrations of the isoflavonoid genistein in androgen-dependent LNCaP cells is mediated by estrogen receptor β [J].

Bektic, J ;

Berger, AP ;

Pfeil, K ;

Dobler, G ;

Bartsch, G ;

Klocker, H .

EUROPEAN UROLOGY, 2004, 45 (02) :245-251

[3] Physiologically achievable concentrations of genistein enhance telomerase activity in prostate cancer cells via the activation of STAT3 [J].

Chau, My N. ;

El Touny, Lara H. ;

Jagadeesh, Shankar ;

Banerjee, Partha P. .

CARCINOGENESIS, 2007, 28 (11) :2282-2290

[4] CCDC62/ERAP75 functions as a coactivator to enhance estrogen receptor beta-mediated transactivation and target gene expression in prostate cancer cells [J].

Chen, Ming ;

Ni, Jing ;

Chang, Hong-Chiang ;

Lin, Chen-Yong ;

Muyan, Mesut ;

Yeh, Shuyuan .

CARCINOGENESIS, 2009, 30 (05) :841-850

[5] The androgen receptor co-activator CBP is up-regulated following androgen withdrawal and is highly expressed in advanced prostate cancer [J].

Comuzzi, B ;

Nemes, C ;

Schmidt, S ;

Jasarevic, Z ;

Lodde, M ;

Pycha, A ;

Bartsch, G ;

Offner, F ;

Culig, Z ;

Hobisch, A .

JOURNAL OF PATHOLOGY, 2004, 204 (02) :159-166

[6] The transcriptional co-activator cAMP response element-binding protein-binding protein is expressed in prostate cancer and enhances androgen- and anti-androgen-induced androgen receptor function [J].

Comuzzi, B ;

Lambrinidis, L ;

Rogatsch, H ;

Godoy-Tundidor, S ;

Knezevic, N ;

Krhen, I ;

Marekovic, Z ;

Bartsch, G ;

Klocker, H ;

Hobisch, A ;

Culig, Z .

AMERICAN JOURNAL OF PATHOLOGY, 2003, 162 (01) :233-241

[7] Switch from antagonist to agonist of the androgen receptor blocker bicalutamide is associated with prostate tumour progression in a new model system [J].

Culig Z. ;

Hoffmann J. ;

Erdel M. ;

Eder I.E. ;

Hobisch A. ;

Hittmair A. ;

Bartsch G. ;

Utermann G. ;

Schneider M.R. ;

Parczyk K. ;

Klocker H. .

British Journal of Cancer, 1999, 81 (2) :242-251

[8] p300 regulates androgen receptor-independent expression of prostate-specific antigen in prostate cancer cells treated chronically with interleukin-6 [J].

Debes, JD ;

Comuzzi, B ;

Schmidt, LJ ;

Dehm, SM ;

Culig, Z ;

Tindall, DJ .

CANCER RESEARCH, 2005, 65 (13) :5965-5973

[9]

Debes JD, 2003, CANCER RES, V63, P7638

[10] Identification of a Biphasic Role for Genistein in the Regulation of Prostate Cancer Growth and Metastasis [J].

El Touny, Lara H. ;

Banerjee, Partha P. .

CANCER RESEARCH, 2009, 69 (08) :3695-3703

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