The androgen receptor: a potential target for therapy of prostate cancer

Santos, Auri Ferreira dos; Huang, Haojie; Tindall, Donald J.

doi:10.1016/j.steroids.2003.10.005

Cited by 65 publications

(48 citation statements)

References 58 publications

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“…AR, an androgen-activated transcription factor, belongs to the steroid nuclear receptor family. Development of the prostate is dependent on androgen signaling mediated through AR, and AR is also important during the development of prostate cancer [16]. LNCaP cells express prostate specific antigen (PSA) upon androgen treatment.…”

Section: Introductionmentioning

confidence: 99%

The liver X receptor agonist T0901317 acts as androgen receptor antagonist in human prostate cancer cells

Chuu

Chen

Hiipakka

et al. 2007

Biochemical and Biophysical Research Communications

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T0901317 is a potent non-steroidal synthetic liver X receptor (LXR) agonist. T0901317 blocked androgenic stimulation of the proliferation of androgen-dependent LNCaP 104-S cells and androgenic suppression of the proliferation of androgen-independent LNCaP 104-R2 cells, inhibited the transcriptional activation of an androgen-dependent reporter gene by androgen, and suppressed gene and protein expression of prostate specific antigen (PSA), a target gene of androgen receptor (AR) without affecting gene and protein expression of AR. T0901317 also inhibited binding of a radiolabeled androgen to AR, but inhibition was much weaker compared to the effect of the antiandrogens, bicalutamide and hydroxyflutamide. The LXR agonist T0901317, therefore, acts as an antiandrogen in human prostate cancer cells.

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Section: Introductionmentioning

confidence: 99%

The liver X receptor agonist T0901317 acts as androgen receptor antagonist in human prostate cancer cells

Chuu

Chen

Hiipakka

et al. 2007

Biochemical and Biophysical Research Communications

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“…AR expression is retained in a significant proportion of AIPC (5,6). Several mechanisms or pathways influence the development of AIPC, allowing the AR to stimulate proliferation even in the absence of androgens.…”

Section: Introductionmentioning

confidence: 99%

Fulvestrant (ICI 182,780) down-regulates androgen receptor expression and diminishes androgenic responses in LNCaP human prostate cancer cells

Bhattacharyya

Krishnan

Swami

et al. 2006

Molecular Cancer Therapeutics

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The androgen receptor (AR) plays a key role in the development and progression of prostate cancer. Targeting the AR for down-regulation would be a useful strategy for treating prostate cancer, especially hormone-refractory or androgen-independent prostate cancer. In the present study, we showed that the antiestrogen fulvestrant [ICI 182,780 (ICI)] effectively suppressed AR expression in several human prostate cancer cells, including androgenindependent cells. In LNCaP cells, ICI (10 Mmol/L) treatment decreased AR mRNA expression by 43% after 24 hours and AR protein expression by f50% after 48 hours. We further examined the mechanism of AR downregulation by ICI in LNCaP cells. ICI did not bind to the T877A-mutant AR present in the LNCaP cells nor did it promote proteasomal degradation of the AR. ICI did not affect AR mRNA or protein half-life. However, ICI decreased the activity of an AR promoter-luciferase reporter plasmid transfected into LNCaP cells, suggesting a direct repression of AR gene transcription. As a result of AR down-regulation by ICI, androgen induction of prostate-specific antigen mRNA and protein expression were substantially attenuated. Importantly, LNCaP cell proliferation was significantly inhibited by ICI treatment. Following 6 days of ICI treatment, a 70% growth inhibition was seen in androgen-stimulated LNCaP cells. These data show that the antiestrogen ICI is a potent AR downregulator that causes significant inhibition of prostate cancer cell growth. Our study suggests that AR downregulation by ICI would be an effective strategy for the treatment of all prostate cancer, especially AR-dependent androgen-independent prostate cancer. [Mol Cancer Ther 2006;5(6):1539 -49]

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“…One of the most troubling aspects of CaP is that, after androgen ablation therapy, androgen-dependent (AD) CaP inevitably progresses to an androgen independent (AI) state, for which no effective treatment has been developed (2). Although several molecular pathways have been invoked to explain the pathogenesis of this disease (3)(4)(5)(6), to date the mechanisms for the development and progression of CaP remain largely unknown.…”

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confidence: 99%

An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells

Shi¹,

Xue²,

Yang³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

428

415

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Although prostate cancer (CaP) is the most frequently diagnosed malignant tumor and the second leading cause of cancer deaths in American men, the mechanisms explaining the development and progression of CaP remain largely unknown. Recent studies have shown that some aberrantly expressed microRNAs (miRNAs) are involved in tumorigenesis. Although aberrant expression of certain miRNAs has been discovered in CaP, their function in this disease has not yet been defined. In this study, we found differential expression of miR-125b in androgen-dependent and independent CaP cells, as well as in benign and malignant prostate tissues. Furthermore, androgen signaling was able to up-regulate the expression of miR-125b. In addition, transfection of synthetic miR-125b stimulated androgen-independent growth of CaP cells and down-regulated the expression of Bak1. Our results suggest that miR-125b acts as an oncogene, contributing to the pathogenesis of CaP.microRNA ͉ miR-125b ͉ ISH ͉ LNCaP

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The androgen receptor: a potential target for therapy of prostate cancer

Cited by 65 publications

References 58 publications

The liver X receptor agonist T0901317 acts as androgen receptor antagonist in human prostate cancer cells

The liver X receptor agonist T0901317 acts as androgen receptor antagonist in human prostate cancer cells

Fulvestrant (ICI 182,780) down-regulates androgen receptor expression and diminishes androgenic responses in LNCaP human prostate cancer cells

An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells

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