Mechanism and Regulation of Gene Expression by Androgen Receptor in Prostate Cancer

2004 ◽  
Author(s):  
Zhengxin Wang
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Regulation Of Gene Expression

scholarly journals Androgen receptor expression is regulated by the phosphoinositide 3-kinase/Akt pathway in normal and tumoral epithelial cells

2002 ◽  
Vol 366 (3) ◽  
pp. 729-736 ◽  
Author(s):  
Michèle MANIN ◽  
Silvère BARON ◽  
Karine GOOSSENS ◽  
Claude BEAUDOIN ◽  
Claude JEAN ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Epithelial Cells ◽  
Regulation Of Gene Expression ◽  
Receptor Expression ◽  
Akt Pathway ◽  
Suitable Model ◽  
Metastatic Prostate Carcinoma ◽  
Phosphoinositide 3 Kinase

The androgen receptor (AR) is a ligand-responsive transcription factor known to play a central role in the pathogenesis of prostate cancer. However, the regulation of AR gene expression in the normal and pathological prostate remains poorly understood. This study focuses on the effect of the phosphoinositide 3-kinase (PI 3-kinase)/Akt axis on AR expression in vas deferens epithelial cells (VDEC), a suitable model to study androgen regulation of gene expression, and LNCaP cells (derived from a metastasis at the left supraclavicular lymph node from a 50-year-old patient with a confirmed diagnosis of metastatic prostate carcinoma). Taken together, our data show for the first time that the PI 3-kinase/Akt pathway is required for basal and dihydrotestosterone-induced AR protein expression in both VDEC and LNCaP. Inhibition of the PI 3-kinase/Akt pathway reduced AR expression and the decline in AR protein level correlated with a decrease in AR mRNA in VDEC but not in LNCaP. Since PI 3-kinase/Akt axis is active in prostate cancer, cross-talk between PI 3-kinase/Akt and AR signalling pathways may have implications for endocrine therapy.

scholarly journals A novel DNA methylation signature is associated with androgen receptor activity and patient prognosis in bone metastatic prostate cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Erik Bovinder Ylitalo ◽  
Elin Thysell ◽  
Mattias Landfors ◽  
Maria Brattsand ◽  
Emma Jernberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Bone Metastases ◽  
Metastatic Prostate Cancer ◽  
Tumor Biology ◽  
Receptor Activity ◽  
Mrna Levels ◽  
Androgen Receptor Activity ◽  
Patient Prognosis

Abstract Background Patients with metastatic prostate cancer (PC) are treated with androgen deprivation therapy (ADT) that initially reduces metastasis growth, but after some time lethal castration-resistant PC (CRPC) develops. A better understanding of the tumor biology in bone metastases is needed to guide further treatment developments. Subgroups of PC bone metastases based on transcriptome profiling have been previously identified by our research team, and specifically, heterogeneities related to androgen receptor (AR) activity have been described. Epigenetic alterations during PC progression remain elusive and this study aims to explore promoter gene methylation signatures in relation to gene expression and tumor AR activity. Materials and methods Genome-wide promoter-associated CpG methylation signatures of a total of 94 tumor samples, including paired non-malignant and malignant primary tumor areas originating from radical prostatectomy samples (n = 12), and bone metastasis samples of separate patients with hormone-naive (n = 14), short-term castrated (n = 4) or CRPC (n = 52) disease were analyzed using the Infinium Methylation EPIC arrays, along with gene expression analysis by Illumina Bead Chip arrays (n = 90). AR activity was defined from expression levels of genes associated with canonical AR activity. Results Integrated epigenome and transcriptome analysis identified pronounced hypermethylation in malignant compared to non-malignant areas of localized prostate tumors. Metastases showed an overall hypomethylation in relation to primary PC, including CpGs in the AR promoter accompanied with induction of AR mRNA levels. We identified a Methylation Classifier for Androgen receptor activity (MCA) signature, which separated metastases into two clusters (MCA positive/negative) related to tumor characteristics and patient prognosis. The MCA positive metastases showed low methylation levels of genes associated with canonical AR signaling and patients had a more favorable prognosis after ADT. In contrast, MCA negative patients had low AR activity associated with hypermethylation of AR-associated genes, and a worse prognosis after ADT. Conclusions A promoter methylation signature classifies PC bone metastases into two groups and predicts tumor AR activity and patient prognosis after ADT. The explanation for the methylation diversities observed during PC progression and their biological and clinical relevance need further exploration.

scholarly journals Reactivation of Androgen Receptor–Regulated TMPRSS2:ERG Gene Expression in Castration-Resistant Prostate Cancer

2009 ◽  
Vol 69 (15) ◽  
pp. 6027-6032 ◽  
Author(s):  
Changmeng Cai ◽  
Hongyun Wang ◽  
Youyuan Xu ◽  
Shaoyong Chen ◽  
Steven P. Balk
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Glucocorticoid Receptor is distinct from Androgen Receptor function in Castrate-Resistant Prostate Cancer

2020 ◽  
Author(s):  
Dalal El-Barbarawi ◽  
Tiha M Long
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Glucocorticoid Receptor ◽  
Gene Expression Analysis ◽  
Target Gene ◽  
Invasive Disease ◽  
Published Data ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Commonly used therapies for prostate cancer (PC) that block androgen receptor (AR) signaling inhibit regrowth, but aggressive castrate-resistant (CR)PC abrogates anti-androgen therapy. Recently published data shows that glucocorticoid receptor (GR) can drive the growth of CRPC when AR is blocked, by mimicking AR activity. Due to the evolution of CRPC into a more invasive disease, we hypothesized that GR-driven CRPC has different activities than AR that promote progression to metastatic disease. To test this hypothesis, we performed gene expression analysis on available datasets to determine which pathways correlate with GR target gene expression. Furthermore, we investigated gene expression in CWR-22Rv1 CRPC cells via qRT-PCR. Our results show that GR-activation in AR-blocked cells induces different genes than AR, suggesting that GR-driven CRPC is unique from AR-driven disease. The scientific contribution of our research may reveal new mechanisms by which GR drives PC progression and unveil novel therapeutic targets.

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