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Endocrine Reviews 25 (2): 276-308
Copyright © 2004 by The Endocrine Society

Androgen Receptor in Prostate Cancer

Cynthia A. Heinlein and Chawnshang Chang

George Whipple Laboratory for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology, and the Cancer Center, University of Rochester, Rochester, New York 14642

Correspondence: Address all correspondence and requests for reprints to: Chawnshang Chang, Ph.D., Department of Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642. E-mail: chang{at}urmc.rochester.edu

The normal development and maintenance of the prostate is dependent on androgen acting through the androgen receptor (AR). AR remains important in the development and progression of prostate cancer. AR expression is maintained throughout prostate cancer progression, and the majority of androgen-independent or hormone refractory prostate cancers express AR. Mutation of AR, especially mutations that result in a relaxation of AR ligand specificity, may contribute to the progression of prostate cancer and the failure of endocrine therapy by allowing AR transcriptional activation in response to antiandrogens or other endogenous hormones. Similarly, alterations in the relative expression of AR coregulators have been found to occur with prostate cancer progression and may contribute to differences in AR ligand specificity or transcriptional activity. Prostate cancer progression is also associated with increased growth factor production and an altered response to growth factors by prostate cancer cells. The kinase signal transduction cascades initiated by mitogenic growth factors modulate the transcriptional activity of AR and the interaction between AR and AR coactivators. The inhibition of AR activity through mechanisms in addition to androgen ablation, such as modulation of signal transduction pathways, may delay prostate cancer progression.




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A Differential Ligand-mediated Response of Green Fluorescent Protein-tagged Androgen Receptor in Living Prostate Cancer and Non-prostate Cancer Cell Lines
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[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
T. I. Klokk, A. Kilander, Z. Xi, H. Waehre, B. Risberg, H. E. Danielsen, and F. Saatcioglu
Kallikrein 4 Is a Proliferative Factor that Is Overexpressed in Prostate Cancer
Cancer Res., June 1, 2007; 67(11): 5221 - 5230.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
J. E. Tillman, J. Yuan, G. Gu, L. Fazli, R. Ghosh, A. S. Flynt, M. Gleave, P. S. Rennie, and S. Kasper
DJ-1 Binds Androgen Receptor Directly and Mediates Its Activity in Hormonally Treated Prostate Cancer Cells
Cancer Res., May 15, 2007; 67(10): 4630 - 4637.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
G. Gu, J. Yuan, M. Wills, and S. Kasper
Prostate Cancer Cells with Stem Cell Characteristics Reconstitute the Original Human Tumor In vivo
Cancer Res., May 15, 2007; 67(10): 4807 - 4815.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
U. Simanainen, C. M. Allan, P. Lim, S. McPherson, M. Jimenez, J. D. Zajac, R. A. Davey, and D. J. Handelsman
Disruption of Prostate Epithelial Androgen Receptor Impedes Prostate Lobe-Specific Growth and Function
Endocrinology, May 1, 2007; 148(5): 2264 - 2272.
[Abstract] [Full Text] [PDF]


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JNCI J Natl Cancer InstHome page
H. Miyamoto, Z. Yang, Y.-T. Chen, H. Ishiguro, H. Uemura, Y. Kubota, Y. Nagashima, Y.-J. Chang, Y.-C. Hu, M.-Y. Tsai, et al.
Promotion of Bladder Cancer Development and Progression by Androgen Receptor Signals
J Natl Cancer Inst, April 4, 2007; 99(7): 558 - 568.
[Abstract] [Full Text] [PDF]


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Molecular Cancer TherapeuticsHome page
J. Guo, C. Jiang, Z. Wang, H.-J. Lee, H. Hu, B. Malewicz, H.-J. Lee, J.-H. Lee, N.-I. Baek, J.-H. Jeong, et al.
A novel class of pyranocoumarin anti-androgen receptor signaling compounds
Mol. Cancer Ther., March 1, 2007; 6(3): 907 - 917.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
C.-M. Chiu, S.-H. Yeh, P.-J. Chen, T.-J. Kuo, C.-J. Chang, P.-J. Chen, W.-J. Yang, and D.-S. Chen
Inaugural Article: Hepatitis B virus X protein enhances androgen receptor-responsive gene expression depending on androgen level
PNAS, February 20, 2007; 104(8): 2571 - 2578.
[Abstract] [Full Text] [PDF]


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J Mol EndocrinolHome page
L. Bonaccorsi, D. Nosi, M. Muratori, L. Formigli, G. Forti, and E. Baldi
Altered endocytosis of epidermal growth factor receptor in androgen receptor positive prostate cancer cell lines
J. Mol. Endocrinol., January 1, 2007; 38(1): 51 - 66.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
S. Srinivasan, R. S. Ranga, R. Burikhanov, S.-S. Han, and D. Chendil
Par-4-Dependent Apoptosis by the Dietary Compound Withaferin A in Prostate Cancer Cells
Cancer Res., January 1, 2007; 67(1): 246 - 253.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
R.-S. Wang, S. Yeh, L.-M. Chen, H.-Y. Lin, C. Zhang, J. Ni, C.-C. Wu, P. A. di Sant'Agnese, K. L. deMesy-Bentley, C.-R. Tzeng, et al.
Androgen Receptor in Sertoli Cell Is Essential for Germ Cell Nursery and Junctional Complex Formation in Mouse Testes
Endocrinology, December 1, 2006; 147(12): 5624 - 5633.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
C. Zhang, S. Yeh, Y.-T. Chen, C.-C. Wu, K.-H. Chuang, H.-Y. Lin, R.-S. Wang, Y.-J. Chang, C. Mendis-Handagama, L. Hu, et al.
Oligozoospermia with normal fertility in male mice lacking the androgen receptor in testis peritubular myoid cells
PNAS, November 21, 2006; 103(47): 17718 - 17723.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
R. Ilagan, J. Pottratz, K. Le, L. Zhang, S. G. Wong, R. Ayala, M. Iyer, L. Wu, S. S. Gambhir, and M. Carey
Imaging Mitogen-Activated Protein Kinase Function in Xenograft Models of Prostate Cancer.
Cancer Res., November 15, 2006; 66(22): 10778 - 10785.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
I. U. Agoulnik, A. Vaid, M. Nakka, M. Alvarado, W. E. Bingman III, H. Erdem, A. Frolov, C. L. Smith, G. E. Ayala, M. M. Ittmann, et al.
Androgens Modulate Expression of Transcription Intermediary Factor 2, an Androgen Receptor Coactivator whose Expression Level Correlates with Early Biochemical Recurrence in Prostate Cancer
Cancer Res., November 1, 2006; 66(21): 10594 - 10602.
[Abstract] [Full Text] [PDF]


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J AndrolHome page
S. Rajender, V. Rajani, N. J. Gupta, B. Chakravarty, L. Singh, and K. Thangaraj
No Association of Androgen Receptor GGN Repeat Length Polymorphism With Infertility in Indian Men
J Androl, November 1, 2006; 27(6): 785 - 789.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
M. M.R. Bhuiyan, Y. Li, S. Banerjee, F. Ahmed, Z. Wang, S. Ali, and F. H. Sarkar
Down-regulation of Androgen Receptor by 3,3'-Diindolylmethane Contributes to Inhibition of Cell Proliferation and Induction of Apoptosis in Both Hormone-Sensitive LNCaP and Insensitive C4-2B Prostate Cancer Cells.
Cancer Res., October 15, 2006; 66(20): 10064 - 10072.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
H. V. Heemers, G. Verhoeven, and J. V. Swinnen
Androgen Activation of the Sterol Regulatory Element-Binding Protein Pathway: Current Insights
Mol. Endocrinol., October 1, 2006; 20(10): 2265 - 2277.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
R. Guo, E. A. Kasbohm, P. Arora, C. J. Sample, B. Baban, N. Sud, P. Sivashanmugam, N. H. Moniri, and Y. Daaka
Expression and Function of Lysophosphatidic Acid LPA1 Receptor in Prostate Cancer Cells
Endocrinology, October 1, 2006; 147(10): 4883 - 4892.
[Abstract] [Full Text] [PDF]


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CarcinogenesisHome page
L.G. Wang, X.M. Liu, and J.W. Chiao
Repression of androgen receptor in prostate cancer cells by phenethyl isothiocyanate
Carcinogenesis, October 1, 2006; 27(10): 2124 - 2132.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
H. Gao, X. Ouyang, W. A. Banach-Petrosky, W. L. Gerald, M. M. Shen, and C. Abate-Shen
Combinatorial activities of Akt and B-Raf/Erk signaling in a mouse model of androgen-independent prostate cancer
PNAS, September 26, 2006; 103(39): 14477 - 14482.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
S. M. Dehm and D. J. Tindall
Ligand-independent Androgen Receptor Activity Is Activation Function-2-independent and Resistant to Antiandrogens in Androgen Refractory Prostate Cancer Cells
J. Biol. Chem., September 22, 2006; 281(38): 27882 - 27893.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
H. Gao, X. Ouyang, W. A. Banach-Petrosky, M. M. Shen, and C. Abate-Shen
Emergence of Androgen Independence at Early Stages of Prostate Cancer Progression in Nkx3.1; Pten Mice
Cancer Res., August 15, 2006; 66(16): 7929 - 7933.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
X.-Y. Dong, C. Chen, X. Sun, P. Guo, R. L. Vessella, R.-X. Wang, L. W.K. Chung, W. Zhou, and J.-T. Dong
FOXO1A Is a Candidate for the 13q14 Tumor Suppressor Gene Inhibiting Androgen Receptor Signaling in Prostate Cancer.
Cancer Res., July 15, 2006; 66(14): 6998 - 7006.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
M. A. Albertelli, A. Scheller, M. Brogley, and D. M. Robins
Replacing the Mouse Androgen Receptor with Human Alleles Demonstrates Glutamine Tract Length-Dependent Effects on Physiology and Tumorigenesis in Mice
Mol. Endocrinol., June 1, 2006; 20(6): 1248 - 1260.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
P. J.M. Hendriksen, N. F.J. Dits, K. Kokame, A. Veldhoven, W. M. van Weerden, C. H. Bangma, J. Trapman, and G. Jenster
Evolution of the Androgen Receptor Pathway during Progression of Prostate Cancer.
Cancer Res., May 15, 2006; 66(10): 5012 - 5020.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
U. K. Misra, R. Deedwania, and S. V. Pizzo
Activation and Cross-talk between Akt, NF-{kappa}B, and Unfolded Protein Response Signaling in 1-LN Prostate Cancer Cells Consequent to Ligation of Cell Surface-associated GRP78
J. Biol. Chem., May 12, 2006; 281(19): 13694 - 13707.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
L. S. Lyons and K. L. Burnstein
Vav3, a Rho GTPase Guanine Nucleotide Exchange Factor, Increases during Progression to Androgen Independence in Prostate Cancer Cells and Potentiates Androgen Receptor Transcriptional Activity
Mol. Endocrinol., May 1, 2006; 20(5): 1061 - 1072.
[Abstract] [Full Text] [PDF]


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Molecular Cancer TherapeuticsHome page
S. M. Hillier, J. C. Marquis, B. Zayas, J. S. Wishnok, R. G. Liberman, P. L. Skipper, S. R. Tannenbaum, J. M. Essigmann, and R. G. Croy
DNA adducts formed by a novel antitumor agent 11{beta}-dichloro in vitro and in vivo.
Mol. Cancer Ther., April 1, 2006; 5(4): 977 - 984.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
R. K. Allan, D. Mok, B. K. Ward, and T. Ratajczak
Modulation of Chaperone Function and Cochaperone Interaction by Novobiocin in the C-terminal Domain of Hsp90: EVIDENCE THAT COUMARIN ANTIBIOTICS DISRUPT Hsp90 DIMERIZATION
J. Biol. Chem., March 17, 2006; 281(11): 7161 - 7171.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
B. He, R. T. Gampe Jr., A. T. Hnat, J. L. Faggart, J. T. Minges, F. S. French, and E. M. Wilson
Probing the Functional Link between Androgen Receptor Coactivator and Ligand-binding Sites in Prostate Cancer and Androgen Insensitivity
J. Biol. Chem., March 10, 2006; 281(10): 6648 - 6663.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
O. Y. Khan, G. Fu, A. Ismail, S. Srinivasan, X. Cao, Y. Tu, S. Lu, and Z. Nawaz
Multifunction Steroid Receptor Coactivator, E6-Associated Protein, Is Involved in Development of the Prostate Gland
Mol. Endocrinol., March 1, 2006; 20(3): 544 - 559.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
C. Jiang, H.-J. Lee, G.-x. Li, J. Guo, B. Malewicz, Y. Zhao, E.-O. Lee, H.-J. Lee, J.-H. Lee, M.-S. Kim, et al.
Potent Antiandrogen and Androgen Receptor Activities of an Angelica gigas-Containing Herbal Formulation: Identification of Decursin as a Novel and Active Compound with Implications for Prevention and Treatment of Prostate Cancer
Cancer Res., January 1, 2006; 66(1): 453 - 463.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
L. Callewaert, N. Van Tilborgh, and F. Claessens
Interplay between Two Hormone-Independent Activation Domains in the Androgen Receptor
Cancer Res., January 1, 2006; 66(1): 543 - 553.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
A. J. Asirvatham, M. Schmidt, B. Gao, and J. Chaudhary
Androgens Regulate the Immune/Inflammatory Response and Cell Survival Pathways in Rat Ventral Prostate Epithelial Cells
Endocrinology, January 1, 2006; 147(1): 257 - 271.
[Abstract] [Full Text] [PDF]


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Endocr. Rev.Home page
D. J. Mulholland, S. Dedhar, G. A. Coetzee, and C. C. Nelson
Interaction of Nuclear Receptors with the Wnt/{beta}-Catenin/Tcf Signaling Axis: Wnt You Like to Know?
Endocr. Rev., December 1, 2005; 26(7): 898 - 915.
[Abstract] [Full Text] [PDF]




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