Two enhancers in one risk region were occupied by AR and responded to androgen treatment; one contained a single nucleotide polymorphism (rs11986220) that resides within a FoxA1 binding site, with the prostate cancer risk allele facilitating both stronger FoxA1 binding and stronger androgen responsiveness.
Thus, this new cell line with partial androgen responsiveness and PSA expression can serve as a functionally relevant model system of bone metastatic prostate cancer, and can be used to investigate the role of AR mutations in prostate cancer and its progression to androgen independence.
In conclusion, our findings highlight novel consequences of constitutively active AR variants on the regulation of mesenchymal markers in prostate cancer.
Using multiple prostate cancer cell lines, we showed that catalytic Topo II inhibitors, ICRF187 and ICRF193 inhibited transcription activities of the wild-type AR, mutant ARs (F876L and W741C) and the AR-V7 splice variant.
Our results suggest that inherited genetic variation in the androgen receptor gene affects hormonal treatment response and ultimately prostate cancer death.
Of these, AR variant-7 may be the most important, and has been implicated in primary resistance to abiraterone and enzalutamide in men with advanced prostate cancer.
The androgen-receptor gene (AR-CAG) repeat length and the percentage of promoter methylation (PPM) of genes glutathione-S-transferase P1 (GSTP1) and Ras association domain family 1 isoform A (RASSF1A) improve PCa detection.
There was a remarkable accumulation of strong RBM3 expression in v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) positive prostate cancers and tumours harbouring PTEN deletions (p<0.0001 each).
The CAG and GGC repeats in the AR have been studied extensively as markers of prostate cancer susceptibility, with inconclusive findings, whereas the AR-E211 G>A polymorphism has been associated with androgenetic alopecia.
The goal was to characterize androgen receptor gene (<i>AR</i>) amplifications and mutations detected in ctDNA from patients with PCa and to further understand the somatic genetic heterogeneity of advanced prostate cancer.
In this review, we will summarize the various alternatively spliced AR variants that have been discovered, with a focus on their role and origin in the pathologic conditions of AIS and PCa.
This study analyzed the polymorphic CAG repeat sequence in exon 1 of the AR gene to determine if the number of repeats might be an indicator of prostate cancer risk or aggressive disease.
The T877A mutant of the AR frequently found in advanced cases of prostate cancer displays an exaggerated stimulation of transcriptional activity by CDK6.
Recently, associations were observed between prostate cancer (CaP) risk and polymorphisms in the vitamin D receptor (VDR) gene and the androgen receptor (AR) gene.
Furthermore, two additional pathological situations are associated with abnormal androgen receptor structure and function -- spinal and bulbar muscular atrophy (SBMA, or Kennedy's disease) and prostate cancer.
When cross-classifying subjects by AR and PSA genotypes, subjects with either a CAG-short allele (and not PSA GG) or with the PSA GG genotype (and not CAG-short) had a modest, statistically insignificant increase in prostate cancer risk overall.