Glyoxalase 2 drives tumorigenesis in human prostate cells in a mechanism involving androgen receptor and p53-p21 axis

2017 ◽  
Vol 56 (9) ◽  
pp. 2112-2126 ◽  
Author(s):  
Cinzia Antognelli ◽  
Ivana Ferri ◽  
Guido Bellezza ◽  
Paola Siccu ◽  
Harold D. Love ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Human Prostate ◽  
Prostate Cells ◽  
Glyoxalase 2

scholarly journals Androgen receptor localisation and turnover in human prostate epithelium treated with the antiandrogen, casodex

2000 ◽  
Vol 24 (3) ◽  
pp. 339-351 ◽  
Author(s):  
AS Waller ◽  
RM Sharrard ◽  
P Berthon ◽  
NJ Maitland
Keyword(s):  
Androgen Receptor ◽  
In Vitro Models ◽  
Human Prostate ◽  
Intracellular Targeting ◽  
Natural Ligand ◽  
Prostate Cells ◽  
Established Cell ◽  
Prostatic Epithelium ◽  
Prostate Epithelium

In vitro models of normal and malignant human prostate are currently limited to a few well established cell lines that, with a single exception (LNCaP), fail to express the androgen receptor (AR) - a common characteristic of prostatic epithelium grown in culture. To investigate the molecular mechanism of action of the non-steroidal antiandrogen Casodex (bicalutamide) against wild-type AR, we have established a transient AR expression model in non-tumorigenic prostate cells of both epithelial and mesenchymal origin. In this model, both dihydrotestosterone and Casodex can effectively transport the AR protein into the nucleus of prostate cells. Whereas the natural ligand, dihydrotestosterone, stabilises the receptor, the AR is rapidly degraded at a nuclear location when the transfected cells are treated with Casodex. In contrast, whereas the mutant AR in the LNCaP line is also degraded on Casodex treatment over the same time period, its intracellular targeting is defective.

scholarly journals CK2 Pro-Survival Role in Prostate Cancer Is Mediated via Maintenance and Promotion of Androgen Receptor and NFκB p65 Expression

2019 ◽  
Vol 12 (2) ◽  
pp. 89
Author(s):  
Janeen H. Trembley ◽  
Betsy T. Kren ◽  
Md. J. Abedin ◽  
Daniel P. Shaughnessy ◽  
Yingming Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Inhibitory Effect ◽  
Strongly Correlated ◽  
Protein Levels ◽  
Small Molecule Inhibition ◽  
Prostate Cells ◽  
Cell Death Response ◽  
Stress Signals ◽  
Castrate Resistant

The prosurvival protein kinase CK2, androgen receptor (AR), and nuclear factor kappa B (NFκB) interact in the function of prostate cells, and there is evidence of crosstalk between these signals in the pathobiology of prostate cancer (PCa). As CK2 is elevated in PCa, and AR and NFκB are involved in the development and progression of prostate cancer, we investigated their interaction in benign and malignant prostate cells in the presence of altered CK2 expression. Our results show that elevation of CK2 levels caused increased levels of AR and NFκB p65 in prostate cells of different phenotypes. Analysis of TCGA PCa data indicated that AR and CK2α RNA expression are strongly correlated. Small molecule inhibition or molecular down-regulation of CK2 caused reduction in AR mRNA expression and protein levels in PCa cells and in orthotopic xenograft tumors by various pathways. Among these, regulation of AR protein stability plays a unifying role in CK2 maintenance of AR protein levels. Our results show induction of various endoplasmic reticulum stress signals after CK2 inhibition, which may play a role in the PCa cell death response. Of note, CK2 inhibition caused loss of cell viability in both parental and enzalutamide-resistant castrate-resistant PCa cells. The present work elucidates the specific link of CK2 to the pathogenesis of PCa in association with AR and NFκB expression; further, the observation that inhibition of CK2 can exert a growth inhibitory effect on therapy-resistant PCa cells emphasizes the potential utility of CK2 inhibition in patients who are on enzalutamide treatment for advanced cancer.

Anti-androgen receptor activity of apoptotic CK2 inhibitor CX4945 in human prostate cancer LNCap cells

2012 ◽  
Vol 22 (17) ◽  
pp. 5470-5474 ◽  
Author(s):  
Byung Jun Ryu ◽  
Seung-hwa Baek ◽  
Jiyeon Kim ◽  
Su Jung Bae ◽  
Sung-Youn Chang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Receptor Activity ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Lncap Cells ◽  
Androgen Receptor Activity ◽  
Ck2 Inhibitor

Immunohistochemistry and in situ hybridization of the androgen receptor in the developing human prostate

1998 ◽  
Vol 197 (3) ◽  
pp. 199-208 ◽  
Author(s):  
G. Aumüller ◽  
Paul-Martin Holterhus ◽  
Lutz Konrad ◽  
Burkhard von Rahden ◽  
Olaf Hiort ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Androgen Receptor ◽  
Human Prostate
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