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JNCI Journal of the National Cancer Institute 2001 93(22):1687-1697; doi:10.1093/jnci/93.22.1687
© 2001 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 93, No. 22, 1687-1697, November 21, 2001
© 2001 Oxford University Press

REVIEW

Androgen Receptor Signaling in Androgen-Refractory Prostate Cancer

Michael E. Grossmann, Haojie Huang, Donald J. Tindall

Affiliations of authors: M. E. Grossmann, H. Huang (Department of Urology), D. J. Tindall (Departments of Urology and Biochemistry/Molecular Biology), Mayo Clinic, Rochester, MN.

Correspondence to: Donald J. Tindall, Ph.D., Departments of Urology and Biochemistry/Molecular Biology, Mayo Clinic, Guggenheim 17, 200 1st St., S.W., Rochester, MN (e-mail: Tindall{at}mayo.edu).

Prostate cancer is the second most prevalent cancer in males in the United States. Standard therapy relies on removing, or blocking the actions of, androgens. In most cases, this therapy results in a regression of the cancer because the prostate and most primary prostate tumors depend on androgens for growth and the avoidance of apoptosis. However, a portion of the cancers eventually relapse, at which point they are termed "androgen refractory" and can no longer be cured by conventional therapy of any type. The precise molecular events that lead from androgen-sensitive prostate cancer to androgen-refractory prostate cancer are, therefore, of great interest. This review seeks to identify specific molecular events that may be linked directly to the progression to androgen-refractory cancer. Some of the mechanisms appear to involve the androgen receptor (AR) directly and include mutations in, or amplification of, the AR gene in a manner that allows the AR to respond to low doses of androgens, other steroids, or antiandrogens. In a less direct manner, coactivators may increase the sensitivity of the AR to androgens and even other nonandrogenic substances through a number of mechanisms. Additional indirect mechanisms that do not result from mutation of the AR may involve activation of the AR by peptide growth factors or cytokines or may involve bypassing the AR entirely via other cellular pathways. Identification of the role of these mechanisms in the progression to androgen-refractory prostate cancer is critical for developing therapies capable of curing this disease.


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Sci. Signal., January 20, 2004; 2004(216): re2 - re2.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. L. Mohler, C. W. Gregory, O. H. Ford III, D. Kim, C. M. Weaver, P. Petrusz, E. M. Wilson, and F. S. French
The Androgen Axis in Recurrent Prostate Cancer
Clin. Cancer Res., January 15, 2004; 10(2): 440 - 448.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
J. D. Debes, T. J. Sebo, C. M. Lohse, L. M. Murphy, D. A. L. Haugen, and D. J. Tindall
p300 in Prostate Cancer Proliferation and Progression
Cancer Res., November 15, 2003; 63(22): 7638 - 7640.
[Abstract] [Full Text] [PDF]

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 Molecular Cancer TherapeuticsHome page
H. Uemura, H. Ishiguro, N. Nakaigawa, Y. Nagashima, Y. Miyoshi, K. Fujinami, A. Sakaguchi, and Y. Kubota
Angiotensin II receptor blocker shows antiproliferative activity in prostate cancer cells: A possibility of tyrosine kinase inhibitor of growth factor
Mol. Cancer Ther., November 1, 2003; 2(11): 1139 - 1147.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. L. Bookout, A. E. Finney, R. Guo, K. Peppel, W. J. Koch, and Y. Daaka
Targeting G{beta}{gamma} Signaling to Inhibit Prostate Tumor Formation and Growth
J. Biol. Chem., September 26, 2003; 278(39): 37569 - 37573.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
T. Hara, K. Nakamura, H. Araki, M. Kusaka, and M. Yamaoka
Enhanced Androgen Receptor Signaling Correlates with the Androgen-refractory Growth in a Newly Established MDA PCa 2b-hr Human Prostate Cancer Cell Subline
Cancer Res., September 1, 2003; 63(17): 5622 - 5628.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
T. W. Marshall, K. A. Link, C. E. Petre-Draviam, and K. E. Knudsen
Differential Requirement of SWI/SNF for Androgen Receptor Activity
J. Biol. Chem., August 15, 2003; 278(33): 30605 - 30613.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
L. Zhang, M. Johnson, K. H. Le, M. Sato, R. Ilagan, M. Iyer, S. S. Gambhir, L. Wu, and M. Carey
Interrogating Androgen Receptor Function in Recurrent Prostate Cancer
Cancer Res., August 1, 2003; 63(15): 4552 - 4560.
[Abstract] [Full Text] [PDF]

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 FASEB J.Home page
P. PAKNESHAN, R. H. XING, and S. A. RABBANI
Methylation status of uPA promoter as a molecular mechanism regulating prostate cancer invasion and growth in vitro and in vivo
FASEB J, June 1, 2003; 17(9): 1081 - 1088.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. M. Rahman, H. Miyamoto, H. Takatera, S. Yeh, S. Altuwaijri, and C. Chang
Reducing the Agonist Activity of Antiandrogens by a Dominant-negative Androgen Receptor Coregulator ARA70 in Prostate Cancer Cells
J. Biol. Chem., May 23, 2003; 278(22): 19619 - 19626.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
E. Baldi, L. Bonaccorsi, and G. Forti
Androgen Receptor: Good Guy or Bad Guy in Prostate Cancer Invasion?
Endocrinology, May 1, 2003; 144(5): 1653 - 1655.
[Full Text] [PDF]

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 Cancer Res.Home page
R. E. Bakin, D. Gioeli, R. A. Sikes, E. A. Bissonette, and M. J. Weber
Constitutive Activation of the Ras/Mitogen-activated Protein Kinase Signaling Pathway Promotes Androgen Hypersensitivity in LNCaP Prostate Cancer Cells
Cancer Res., April 15, 2003; 63(8): 1981 - 1989.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
D. Farini, A. Puglianiello, C. Mammi, G. Siracusa, and C. Moretti
Dual Effect of Pituitary Adenylate Cyclase Activating Polypeptide on Prostate Tumor LNCaP Cells: Short- and Long-Term Exposure Affect Proliferation and Neuroendocrine Differentiation
Endocrinology, April 1, 2003; 144(4): 1631 - 1643.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
A. Santamaria, P. L. Fernandez, X. Farre, P. Benedit, J. Reventos, J. Morote, R. Paciucci, and T. M. Thomson
PTOV-1, a Novel Protein Overexpressed in Prostate Cancer, Shuttles between the Cytoplasm and the Nucleus and Promotes Entry into the S Phase of the Cell Division Cycle
Am. J. Pathol., March 1, 2003; 162(3): 897 - 905.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
R. M. Adam, J. Kim, J. Lin, A. Orsola, L. Zhuang, D. C. Rice, and M. R. Freeman*
Heparin-Binding Epidermal Growth Factor-Like Growth Factor Stimulates Androgen-Independent Prostate Tumor Growth and Antagonizes Androgen Receptor Function
Endocrinology, December 1, 2002; 143(12): 4599 - 4608.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
J. D. Debes, L. J. Schmidt, H. Huang, and D. J. Tindall
p300 Mediates Androgen-independent Transactivation of the Androgen Receptor by Interleukin 6
Cancer Res., October 15, 2002; 62(20): 5632 - 5636.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
I. K. Mellinghoff, C. Tran, and C. L. Sawyers
Growth Inhibitory Effects of the Dual ErbB1/ErbB2 Tyrosine Kinase Inhibitor PKI-166 on Human Prostate Cancer Xenografts
Cancer Res., September 15, 2002; 62(18): 5254 - 5259.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
L. Xia, D. Robinson, A.-H. Ma, H.-C. Chen, F. Wu, Y. Qiu, and H.-J. Kung
Identification of Human Male Germ Cell-associated Kinase, a Kinase Transcriptionally Activated by Androgen in Prostate Cancer Cells
J. Biol. Chem., September 13, 2002; 277(38): 35422 - 35433.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
J. Simard, M. Dumont, P. Soucy, and F. Labrie
Perspective: Prostate Cancer Susceptibility Genes
Endocrinology, June 1, 2002; 143(6): 2029 - 2040.
[Full Text] [PDF]

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 Molecular Cancer TherapeuticsHome page
Y. B. Wetherill, C. E. Petre, K. R. Monk, A. Puga, and K. E. Knudsen
The Xenoestrogen Bisphenol A Induces Inappropriate Androgen Receptor Activation and Mitogenesis in Prostatic Adenocarcinoma Cells
Mol. Cancer Ther., May 1, 2002; 1(7): 515 - 524.
[Abstract] [Full Text] [PDF]


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