scholarly journals Reciprocal feedback inhibition of the androgen receptor and PI3K as a novel therapy for castrate-sensitive and -resistant prostate cancer

Oncotarget ◽  
2015 ◽  
Vol 6 (39) ◽  
pp. 41976-41987 ◽  
Author(s):  
Wenqing Qi ◽  
Carla Morales ◽  
Laurence S. Cooke ◽  
Benny Johnson ◽  
Bradley Somer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Feedback Inhibition ◽  
Novel Therapy

scholarly journals Chromatin-directed proteomics-identified network of endogenous androgen receptor in prostate cancer cells

Oncogene ◽  
2021 ◽  
Author(s):  
Kaisa-Mari Launonen ◽  
Ville Paakinaho ◽  
Gianluca Sigismondo ◽  
Marjo Malinen ◽  
Reijo Sironen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Protein A ◽  
Chorioallantoic Membrane ◽  
Chromatin Accessibility ◽  
Castration Resistant Prostate Cancer ◽  
Novel Therapy ◽  
Mesenchymal Transition

AbstractTreatment of prostate cancer confronts resistance to androgen receptor (AR)-targeted therapies. AR-associated coregulators and chromatin proteins hold a great potential for novel therapy targets. Here, we employed a powerful chromatin-directed proteomics approach termed ChIP-SICAP to uncover the composition of chromatin protein network, the chromatome, around endogenous AR in castration resistant prostate cancer (CRPC) cells. In addition to several expected AR coregulators, the chromatome contained many nuclear proteins not previously associated with the AR. In the context of androgen signaling in CRPC cells, we further investigated the role of a known AR-associated protein, a chromatin remodeler SMARCA4 and that of SIM2, a transcription factor without a previous association with AR. To understand their role in chromatin accessibility and AR target gene expression, we integrated data from ChIP-seq, RNA-seq, ATAC-seq and functional experiments. Despite the wide co-occurrence of SMARCA4 and AR on chromatin, depletion of SMARCA4 influenced chromatin accessibility and expression of a restricted set of AR target genes, especially those involved in cell morphogenetic changes in epithelial-mesenchymal transition. The depletion also inhibited the CRPC cell growth, validating SMARCA4’s functional role in CRPC cells. Although silencing of SIM2 reduced chromatin accessibility similarly, it affected the expression of a much larger group of androgen-regulated genes, including those involved in cellular responses to external stimuli and steroid hormone stimulus. The silencing also reduced proliferation of CRPC cells and tumor size in chick embryo chorioallantoic membrane assay, further emphasizing the importance of SIM2 in CRPC cells and pointing to the functional relevance of this potential prostate cancer biomarker in CRPC cells. Overall, the chromatome of AR identified in this work is an important resource for the field focusing on this important drug target.

Dual targeting of EZH2 and androgen receptor as a novel therapy for castration-resistant prostate cancer

2020 ◽  
Vol 404 ◽  
pp. 115200 ◽  
Author(s):  
Eswar Shankar ◽  
Daniel Franco ◽  
Omair Iqbal ◽  
Stephen Moreton ◽  
Rajnee Kanwal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Castration Resistant Prostate Cancer ◽  
Novel Therapy ◽  
Castration Resistant ◽  
Dual Targeting

scholarly journals Expression of GnRH type II is regulated by the androgen receptor in prostate cancer

2007 ◽  
Vol 14 (3) ◽  
pp. 613-624 ◽  
Author(s):  
S Darby ◽  
J Stockley ◽  
M M Khan ◽  
C N Robson ◽  
H Y Leung ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cell Lines ◽  
Xenograft Model ◽  
Direct Interaction ◽  
Upstream Region ◽  
Lncap Cells ◽  
Novel Therapy ◽  
Pc3 Cells ◽  
And Migration

GnRH II has important functional effects in steroid hormone-dependent tumours. Here we investigated the expression and regulation of GnRH II in prostate cancer. GnRH II protein was equally expressed in benign (73%) and malignant (78%) biopsies studied in a prostate tissue microarray (P = 0.779). There was no relationship between expression and clinical parameters in the cancer cohort. GnRH II was, however, significantly reduced in tumour biopsies following hormone ablation. This was further investigated in a prostate xenograft model where androgens increased GnRH II levels, while their withdrawal reduced it. In cell lines, we confirmed high levels of GnRH II in androgen receptor (AR)-positive LNCaP cells but low levels in AR-negative PC3 cells. In LNCaP cells, GnRH II induction by androgens was blocked by the AR inhibitor casodex, but not by cycloheximide treatment. Sequence analysis subsequently revealed a putative androgen response element in the upstream region of the GnRH II gene and direct interaction with the AR was confirmed in chromatin immunoprecipitation experiments. Finally, to test whether the effects of GnRH II were dependent on AR expression, LNCaP and PC3 cells were exposed to exogenous peptide. In both cell lines, GnRH II inhibited cell proliferation and migration, suggesting that its function is independent of AR status. These results provide evidence that GnRH II is widely expressed in prostate cancer and is an AR-regulated gene. Further studies are warranted to characterise the effects of GnRH II on prostate cancer cells and investigate its potential value as a novel therapy.

609: Effects of Sirna and Phytoestrogen Treatments on the Expression of Genes Regulated through the Androgen Receptor of Lncap Prostate Cancer Cells

2004 ◽  
Vol 171 (4S) ◽  
pp. 162-162
Author(s):  
Paul Thelen ◽  
Michal Grzmil ◽  
Iris E. Eder ◽  
Barbara Spengler ◽  
Peter Burfeind ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Expression Of Genes
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