Abstract 4809: Bardoxolone-methyl suppresses both androgen receptor and its splice-variant ARv7 in prostate cancer cells to enhance the anti-cancer efficacy of enzalutamide

Author(s):  
Namrata Khurana ◽  
Partha Chandra ◽  
Hogyoung Kim ◽  
Asim B Abdel-Mageed ◽  
Suresh Sikka ◽  
...  
2021 ◽  
Vol 32 ◽  
pp. S1367
Author(s):  
A.M. Scherbakov ◽  
M. Barysevich ◽  
M. Laktsevich-Iskryk ◽  
O.E. Andreeva ◽  
D.V. Sorokin ◽  
...  

2011 ◽  
Vol 286 (41) ◽  
pp. 36152-36160 ◽  
Author(s):  
Xi Yang ◽  
Zhiyong Guo ◽  
Feng Sun ◽  
Wei Li ◽  
Alan Alfano ◽  
...  

Progression from the androgen-sensitive to androgen-insensitive (or castration-resistant) stage is the major obstacle for sustained effectiveness of hormonal therapy for prostate cancer. The androgen receptor (AR) and its splice variants play important roles in regulating the transcription program essential for castration resistance. Here, we report the identification of a novel AR splice variant, designated as AR8, which is up-regulated in castration-resistant prostate cancer cells. AR8 is structurally different from other known AR splice variants because it lacks a DNA binding domain and therefore, unlikely functions as a transcription factor on its own. Immunofluorescence staining revealed that AR8 was primarily localized on the plasma membrane, possibly through palmitoylation of two cysteine residues within its unique C-terminal sequence. Mutation of these putative palmitoylation sites in AR8 led to loss of its plasma membrane localization. In addition, we demonstrated that overexpression of AR8 in prostate cancer cells promoted association of Src and AR with the EGF receptor in response to EGF treatment and enhanced tyrosine phosphorylation of AR. Conversely, specific knockdown of AR8 expression in prostate cancer cells compromised EGF-induced Src activation and AR phosphorylation. This effect was accompanied with attenuation of proliferation and increased apoptosis in prostate cancer cells cultured in androgen-depleted medium. We also showed that AR8 was required for optimal transcriptional activity of AR in response to treatment of both androgen and EGF. Taken together, our results demonstrate that the membrane-associated AR8 isoform may contribute to castration resistance by potentiating AR-mediated proliferative and survival responses to hormones and growth factors.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manjul Rana ◽  
Jianrong Dong ◽  
Matthew J. Robertson ◽  
Paul Basil ◽  
Cristian Coarfa ◽  
...  

An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Oncotarget ◽  
2015 ◽  
Vol 6 (31) ◽  
pp. 31997-32012 ◽  
Author(s):  
Ayesha A. Shafi ◽  
Vasanta Putluri ◽  
James M. Arnold ◽  
Efrosini Tsouko ◽  
Suman Maity ◽  
...  

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