scholarly journals Influence of stromal–epithelial interactions on androgen action

2014 ◽  
Vol 21 (4) ◽  
pp. T147-T160 ◽  
Author(s):  
Cera M Nieto ◽  
Leah C Rider ◽  
Scott D Cramer
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Normal Development ◽  
Differentially Expressed ◽  
Androgen Action ◽  
Autocrine Control ◽  
And Function ◽  
Mammary Tissues

Androgen receptor (AR) signaling is vital to the development and function of the prostate and is a key pathway in prostate cancer. AR is differentially expressed in the stroma and epithelium, with both paracrine and autocrine control throughout the prostate. Stromal–epithelial interactions within the prostate are commonly dependent on AR signaling and expression. Alterations in these pathways can promote tumorigenesis. AR is also expressed in normal and malignant mammary tissues. Emerging data indicate a role for AR in certain subtypes of breast cancer that has the potential to be exploited therapeutically. The aim of this review is to highlight the importance of these interactions in normal development and tumorigenesis, with a focus on the prostate and breast.

scholarly journals Androgen receptor knockout and knock-in mouse models

2008 ◽  
Vol 42 (1) ◽  
pp. 11-17 ◽  
Author(s):  
S Kerkhofs ◽  
S Denayer ◽  
A Haelens ◽  
F Claessens
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Steroid Hormones ◽  
Mouse Models ◽  
Reproductive Development ◽  
Androgen Insensitivity Syndrome ◽  
Androgen Insensitivity ◽  
And Function ◽  
Insight Into ◽  
Working Mechanisms

Androgens play an important role in male reproductive development and function. These steroid hormones mediate their actions by binding to the androgen receptor (AR). Diseases such as androgen insensitivity syndrome, prostate cancer, Kennedy's disease, and infertility can be caused by mutations in the AR. To get a better insight into the molecular working mechanisms of the AR, several knockout and knock-in mouse models have been developed. These models are reviewed here and are compared with human diseases.

scholarly journals Androgen receptor moonlighting in the prostate cancer microenvironment

2018 ◽  
Vol 25 (6) ◽  
pp. R331-R349 ◽  
Author(s):  
B Cioni ◽  
W Zwart ◽  
A M Bergman
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Normal Development ◽  
Protective Role ◽  
Biological Action ◽  
Prostate Cells ◽  
Classical Function ◽  
Biological Literature

Androgen receptor (AR) signaling is vital for the normal development of the prostate and is critically involved in prostate cancer (PCa). AR is not only found in epithelial prostate cells but is also expressed in various cells in the PCa-associated stroma, which constitute the tumor microenvironment (TME). In the TME, AR is expressed in fibroblasts, macrophages, lymphocytes and neutrophils. AR expression in the TME was shown to be decreased in higher-grade and metastatic PCa, suggesting that stromal AR plays a protective role against PCa progression. With that, the functionality of AR in stromal cells appears to deviate from the receptor’s classical function as described in PCa cells. However, the biological action of AR in these cells and its effect on cancer progression remains to be fully understood. Here, we systematically review the pathological, genomic and biological literature on AR actions in various subsets of prostate stromal cells and aim to better understand the consequences of AR signaling in the TME in relation to PCa development and progression.

scholarly journals Androgen receptor antagonists for prostate cancer therapy

2014 ◽  
Vol 21 (4) ◽  
pp. T105-T118 ◽  
Author(s):  
Christine Helsen ◽  
Thomas Van den Broeck ◽  
Arnout Voet ◽  
Stefan Prekovic ◽  
Hendrik Van Poppel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Practice ◽  
Androgen Receptor ◽  
Metastatic Prostate Cancer ◽  
Castration Resistant ◽  
Androgen Action ◽  
Conflicting Evidence ◽  
Prostate Cancer Therapy ◽  
Androgen Receptor Antagonists

Androgen deprivation is the mainstay therapy for metastatic prostate cancer (PCa). Another way of suppressing androgen receptor (AR) signaling is via AR antagonists or antiandrogens. Despite being frequently prescribed in clinical practice, there is conflicting evidence concerning the role of AR antagonists in the management of PCa. In the castration-resistant settings of PCa, docetaxel has been the only treatment option for decades. With recent evidence that castration-resistant PCa is far from AR-independent, there has been an increasing interest in developing new AR antagonists. This review gives a concise overview of the clinically available antiandrogens and the experimental AR antagonists that tackle androgen action with a different approach.

Interaction mechanism exploration of R-bicalutamide/S-1 with WT/W741L AR using molecular dynamics simulations

2015 ◽  
Vol 11 (12) ◽  
pp. 3347-3354 ◽  
Author(s):  
Hongli Liu ◽  
Xiaoli An ◽  
Shuyan Li ◽  
Yuwei Wang ◽  
Jiazhong Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Dynamics ◽  
Androgen Receptor ◽  
Molecular Dynamics Simulations ◽  
First Generation ◽  
Interaction Mechanism ◽  
Androgen Action ◽  
Treat Prostate Cancer ◽  
Dynamics Simulations

R-Bicalutamide is a first generation antiandrogen used to treat prostate cancer, which inhibits androgen action by competitively binding to the androgen receptor (AR).

scholarly journals Development and Function of the Adult Generation of Leydig Cells in Mice with Sertoli Cell-Selective or Total Ablation of the Androgen Receptor

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 4117-4126 ◽  
Author(s):  
Karel De Gendt ◽  
Nina Atanassova ◽  
Karen A. L. Tan ◽  
Luiz Renato de França ◽  
Gleydes Gambogi Parreira ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Growth Factor ◽  
Sertoli Cell ◽  
Leydig Cells ◽  
Platelet Derived Growth Factor ◽  
Testosterone Levels ◽  
Androgen Action ◽  
Serum Lh ◽  
D 12 ◽  
And Function

Abstract It is established that androgens and unidentified Sertoli cell (SC)-derived factors can influence the development of adult Leydig cells (LC) in rodents, but the mechanisms are unclear. We evaluated adult LC development and function in SC-selective androgen receptor (AR) knockout (SCARKO) and complete AR knockout (ARKO) mice. In controls, LC number increased 26-fold and LC size increased by approximately 2-fold between 12 and 140 d of age. LC number in SCARKOs was normal on d 12, but was reduced by more than 40% at later ages, although LC were larger and contained more lipid droplets and mitochondria than control LC by adulthood. ARKO LC number was reduced by up to 83% at all ages compared with controls, and LC size did not increase beyond d 12. Serum LH and testosterone levels and seminal vesicle weights were comparable in adult SCARKOs and controls, whereas LH levels were elevated 8-fold in ARKOs, although testosterone levels appeared normal. Immunohistochemistry and quantitative PCR for LC-specific markers indicated steroidogenic function per LC was probably increased in SCARKOs and reduced in ARKOs. In SCARKOs, insulin-like factor-3 and estrogen sulfotransferase (EST) mRNA expression were unchanged and increased 3-fold, respectively, compared with controls, whereas the expression of both was reduced more than 90% in ARKOs. Changes in EST expression, coupled with reduced platelet-derived growth factor-A expression, are potential causes of altered LC number and function in SCARKOs. These results show that loss of androgen action on SC has major consequences for LC development, and this could be mediated indirectly via platelet-derived growth factor-A and/or estrogens/EST.

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