Contribution of the androgen receptor to prostate cancer predisposition and progression

Buchanan, Grant; Irvine, Ryan A.; Coetzee, Gerhard A.; Tilley, Wayne D.

doi:10.1007/0-306-48143-x_6

Cited by 67 publications

(100 citation statements)

References 109 publications

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“…AR is expressed throughout prostate cancer progression and its expression persists in the majority of patients with hormone-refractory disease (Cunha et al, 1987;Sadi et al, 1991;van der Kwast et al, 1991;Chodak et al, 1992;Hobisch et al, 1996;Mohler et al, 1996;Buchanan et al, 2001), and many AR mutations identified from hormone-refractory prostate tumors are capable of transactivation. These observations suggest that the eventual failure of ADT cannot be attributed simply to the loss of AR function.…”

Section: Introductionmentioning

confidence: 99%

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

et al. 2010

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Prostate cancer is one of the major causes of cancerrelated death in the western world. Androgen-deprivation therapy (ADT) for the suppression of androgens binding to the androgen receptor (AR) has been the norm of prostate cancer treatment. Despite early success to suppress prostate tumor growth, ADT eventually fails leading to recurrent tumor growth in a hormonerefractory manner, even though AR remains to function in hormone-refractory prostate cancer. Interestingly, some prostate cancer survivors who received androgen replacement therapy had improved quality of life without adverse effect on their cancer progression. These contrasting clinical data suggest that differential androgen/ AR signals in individual cells of prostate tumors can exist in the same or different patients, and may be used to explain why ADT of prostate cancer fails. Such a hypothesis is supported by the results obtained from transgenic mice with selective knockout of AR in prostatic stromal vs epithelial cells and orthotopic transplants of various human prostate cancer cell lines with AR overexpression or knockout. These studies concluded that AR functions as a stimulator for prostate cancer proliferation and metastasis in stromal cells, as a survival factor of prostatic cancer epithelial luminal cells, and as a suppressor for prostate cancer basal intermediate cell growth and metastasis. These dual yet opposite functions of the stromal and epithelial AR may challenge the current ADT to battle prostate cancer and should be taken into consideration when developing new AR-targeting therapies in selective prostate cancer cells.

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Section: Introductionmentioning

confidence: 99%

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

et al. 2010

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“…In this study, we investigated the mechanism of AR ubiquitin-mediated degradation prompted by PAK6 in the presence of androgen. Both PAK6 and AR are highly expressed in prostate cancer (2,8,26), although the correlation between PAK6 and AR in prostate cancer has not yet been reported. To the best of our knowledge, this study is the first to show that AR co-localized with PAK6 in the cytoplasm of prostate epithelial cells and translocated into the nucleus of malignant prostate cells (Fig.…”

Section: Discussionmentioning

confidence: 95%

“…PAK6 and AR are highly expressed in prostate cancer (2,8,26). To investigate the relationship between PAK6 and AR in prostate and cancer tissues, 14 normal prostatic tissues and 23 prostatic adenocarcinoma samples were analyzed by immunofluorescence staining.…”

Section: Pak6 Involvement In Ar Localization and Expression-mentioning

confidence: 99%

“…The androgen receptor (AR), 2 a well known transcription factor, generally regulates gene expression through a ligand-dependent mechanism. The androgen receptor signaling pathway plays an essential role in the development, function, and balance of the androgen response system, especially for the growth and development of normal prostate and cancer cells, as well as in recurrent prostate cancer after androgen ablation therapy (1)(2)(3)(4).…”

mentioning

confidence: 99%

“…The androgen receptor signaling pathway plays an essential role in the development, function, and balance of the androgen response system, especially for the growth and development of normal prostate and cancer cells, as well as in recurrent prostate cancer after androgen ablation therapy (1)(2)(3)(4). Moreover, animal and human models showed that AR expression positively correlated with progression of primary and metastatic prostate cancer (5,6).…”

mentioning

confidence: 99%

See 2 more Smart Citations

p21-activated Kinase 6 (PAK6) Inhibits Prostate Cancer Growth via Phosphorylation of Androgen Receptor and Tumorigenic E3 Ligase Murine Double Minute-2 (Mdm2)

Liu

et al. 2013

Journal of Biological Chemistry

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Background: Deregulation of AR signaling may lead to prostate cancer. Results: PAK6 promotes AR ubiquitin-mediated degradation through phosphorylation of AR and Mdm2, resulting in inhibition of prostate cancer growth in vivo. Conclusion: PAK6 suppresses prostate cancer growth via regulating AR homeostasis. Significance: Modulating PAK6 kinase activity is a therapeutic strategy for AR-positive and hormone-sensitive prostate cancer.

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Androgen receptor coregulators and their involvement in the development and progression of prostate cancer

Chmelar

Buchanan

Need

et al. 2006

Intl Journal of Cancer

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215

191

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The androgen receptor signaling axis plays an essential role in the development, function and homeostasis of male urogenital structures including the prostate gland although the mechanism by which the AR axis contributes to the initiation, progression and metastatic spread of prostate cancer remains somewhat enigmatic. A number of molecular events have been proposed to act at the level of the AR and associated coregulators to influence the natural history of prostate cancer including deregulated expression, somatic mutation, and post-translational modification. The purpose of this article is to review the evidence for deregulated expression and function of the AR and associated coactivators and corepressors and how such events might contribute to the progression of prostate cancer by controlling the selection and expression of AR targets. ' 2006 Wiley-Liss, Inc.

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Contribution of the androgen receptor to prostate cancer predisposition and progression

Cited by 67 publications

References 109 publications

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

p21-activated Kinase 6 (PAK6) Inhibits Prostate Cancer Growth via Phosphorylation of Androgen Receptor and Tumorigenic E3 Ligase Murine Double Minute-2 (Mdm2)

Androgen receptor coregulators and their involvement in the development and progression of prostate cancer

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