scholarly journals RELA is sufficient to mediate interleukin‐1 repression of androgen receptor expression and activity in an LNCaP disease progression model

The Prostate ◽  
2019 ◽  
Vol 80 (2) ◽  
pp. 133-145 ◽  
Author(s):  
Shayna E. Thomas‐Jardin ◽  
Haley Dahl ◽  
Mohammed S. Kanchwala ◽  
Freedom Ha ◽  
Joan Jacob ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Disease Progression ◽  
Interleukin 1 ◽  
Receptor Expression ◽  
Androgen Receptor Expression ◽  
Progression Model ◽  
Disease Progression Model ◽  
Expression And Activity

scholarly journals Prostate cancer cells tolerate a narrow range of androgen receptor expression and activity

The Prostate ◽  
2007 ◽  
Vol 67 (16) ◽  
pp. 1801-1815 ◽  
Author(s):  
Natalia D. Tararova ◽  
Natalya Narizhneva ◽  
Vadim Krivokrisenko ◽  
Andrei V. Gudkov ◽  
Katerina V. Gurova
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Narrow Range ◽  
Receptor Expression ◽  
Androgen Receptor Expression ◽  
Prostate Cancer Cells ◽  
Expression And Activity

scholarly journals RELA is Sufficient to Mediate Interleukin-1 (IL-1) Repression of Androgen Receptor Expression and Activity in LNCaP Disease Progression Model

2019 ◽  
Author(s):  
Shayna E. Thomas-Jardin ◽  
Haley Dahl ◽  
Mohammed S. Kanchwala ◽  
Freedom Ha ◽  
Joan Jacob ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Androgen Receptor ◽  
Disease Progression ◽  
Cell Lines ◽  
Pathway Analysis ◽  
Molecular Mechanisms ◽  
Interleukin 1 ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Lncap Cells

ABSTRACTBackgroundThe Androgen Receptor (AR) nuclear transcription factor is a therapeutic target for prostate cancer (PCa). Unfortunately, patients can develop resistance to AR-targeted therapies and progress to lethal disease, underscoring the importance of understanding the molecular mechanisms that underlie treatment resistance. Inflammation is implicated in PCa initiation and progression and we have previously reported that the inflammatory cytokine, interleukin-1 (IL-1), represses AR mRNA levels and activity in AR-positive (AR+) PCa cell lines concomitant with the upregulation of pro-survival biomolecules. Thus, we contend that IL-1 can select for AR-independent, treatment-resistant PCa cells.MethodsTo begin to explore how IL-1 signaling leads to the repression of AR mRNA levels, we performed comprehensive pathway analysis on our RNA sequencing data from IL-1-treated LNCaP PCa cells. Our pathway analysis predicted Nuclear Factor Kappa B (NF-κB) p65 subunit (RELA), a canonical IL-1 signal transducer, to be significantly active and potentially regulate many genes, including AR. We used siRNA to silence the NF-κB family of transcription factor subunits, RELA, RELB, c-REL, NFKB1, or NFKB2, in IL-1-treated LNCaP, C4-2, and C4-2B PCa cell lines. C4-2 and C4-2B cell lines are castration-resistant LNCaP sublines and represent progression towards metastatic PCa disease; and we have previously shown that IL-1 represses AR mRNA levels in C4-2 and C4-2B cells.ResultssiRNA revealed that RELA alone is sufficient to mediate IL-1 repression of AR mRNA and AR activity. Intriguingly, while LNCaP cells are more sensitive to IL-1-mediated repression of AR than C4-2 and C4-2B cells, RELA siRNA led to a more striking de-repression of AR mRNA levels and AR activity in C4-2 and C4-2B cells than in LNCaP cells.ConclusionsThese data indicate that there are RELA-independent mechanisms that regulate IL-1-mediated AR repression in LNCaP cells and suggest that the switch to RELA-dependent IL-1 repression of AR in C4-2 and C4-2B cells reflects changes in epigenetic and transcriptional programs that evolve during PCa disease progression.

Androgen receptor expression in normal, hyperplastic and neoplastic hepatoid glands in the dog

2006 ◽  
Vol 81 (2) ◽  
pp. 231-236 ◽  
Author(s):  
G. Pisani ◽  
F. Millanta ◽  
D. Lorenzi ◽  
I. Vannozzi ◽  
A. Poli
Keyword(s):  
Androgen Receptor ◽  
Receptor Expression ◽  
Androgen Receptor Expression
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