Partners in crime: deregulation of AR activity and androgen synthesis in prostate cancer

被引：232

作者：

Knudsen, Karen E. ^{[1
,2
]}

Penning, Trevor M. ^{[3
]}

机构：

[1] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA

[2] Thomas Jefferson Univ, Dept Urol, Philadelphia, PA 19107 USA

[3] Univ Penn, Sch Med, Ctr Excellence Environm Toxicol, Dept Pharmacol, Philadelphia, PA 19104 USA

来源：

TRENDS IN ENDOCRINOLOGY AND METABOLISM | 2010年 / 21卷 / 05期

基金：

美国国家卫生研究院;

关键词：

RECEPTOR GENE AMPLIFICATION; SELECTIVE INHIBITOR; PROTEIN EXPRESSION; SPLICE VARIANT; HORMONE; TRANSCRIPTION; PROGRESSION; RISK; IDENTIFICATION; TESTOSTERONE;

D O I：

10.1016/j.tem.2010.01.002

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Prostate cancer remains a leading cause of cancer death, as there are no durable means to treat advanced disease. Treatment of non-organ-confined prostate cancer hinges on its androgen dependence. First-line therapeutic strategies suppress androgen receptor (AR) activity, via androgen ablation and direct AR antagonists, whereas initially effective, incurable, 'castration-resistant' tumors arise as a result of resurgent AR activity. Alterations of AR and/or associated regulatory networks are known to restore receptor activity and support resultant therapy-resistant tumor progression. However, recent evidence also reveals an unexpected contribution of the AR ligand, indicating that alterations in pathways controlling androgen synthesis support castration-resistant AR activity. In this report, the mechanisms underlying the lethal pairing of AR deregulation and aberrant androgen synthesis in prostate cancer progression will be discussed.

引用

页码：315 / 324

页数：10

共 94 条

[1]

Agoulnik IU, 2008, ADV EXP MED BIOL, V617, P245, DOI 10.1007/978-0-387-69080-3_23

[2] 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

[3] Prostate cancer cell cycle regulators: Response to androgen withdrawal and development of androgen independence [J].

Agus, DB ;

Cordon-Cardo, C ;

Fox, W ;

Drobnjak, M ;

Koff, A ;

Golde, DW ;

Scher, HI .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1999, 91 (21) :1869-1876

[4] Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency [J].

Andersson, S ;

Geissler, WM ;

Wu, L ;

Davis, DL ;

Grumbach, MM ;

New, MJ ;

Schwarz, HP ;

Blethen, SL ;

Mendonca, BB ;

Bloise, W ;

Witchel, SF ;

Cutler, GB ;

Griffin, JE ;

Wilson, JD ;

Russell, DW .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1996, 81 (01) :130-136

[5] THE MOLECULAR-BIOLOGY OF ANDROGENIC 17-BETA-HYDROXYSTEROID DEHYDROGENASES [J].

ANDERSSON, S ;

GEISSLER, WM ;

PATEL, S ;

WU, L .

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1995, 53 (1-6) :37-39

[6] Castration-Resistant Prostate Cancer: Locking Up the Molecular Escape Routes [J].

Attar, Ricardo M. ;

Takimoto, Chris H. ;

Gottardis, Marco M. .

CLINICAL CANCER RESEARCH, 2009, 15 (10) :3251-3255

[7] Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven [J].

Attard, Gerhardt ;

Reid, Alison H. M. ;

Yap, Timothy A. ;

Raynaud, Florence ;

Dowsett, Mitch ;

Settatree, Sarah ;

Barrett, Mary ;

Parker, Christopher ;

Martins, Vanessa ;

Folkerd, Elizabeth ;

Clark, Jeremy ;

Cooper, Colin S. ;

Kaye, Stan B. ;

Dearnaley, David ;

Lee, Gloria ;

de Bono, Johann S. .

JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (28) :4563-4571

[8] The backdoor pathway to dihydrotestosterone [J].

Auchus, RJ .

TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2004, 15 (09) :432-438

[9]

Balk Steven P, 2008, Nucl Recept Signal, V6, pe001, DOI 10.1621/nrs.06001

[10] Identification of the major oxidative 3α-hydroxysteroid dehydrogenase in human prostate that converts 5α-androstane-3α,17β-diol to 5α-dihydrotestosterone:: A potential therapeutic target for androgen-dependent disease [J].

Bauman, DR ;

Steckelbroeck, S ;

Williams, MV ;

Peehl, DM ;

Penning, TM .

MOLECULAR ENDOCRINOLOGY, 2006, 20 (02) :444-458

← 1 2 3 4 5 6 7 8 9 10 →