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Proceedings 2018, 2(25), 1580; https://doi.org/10.3390/proceedings2251580

Nutlin3a Contributes to the Cytoplasmic Retention of Androgen Receptor

1
Department of Bioengineering, Faculty of Engineering, Ege University, Izmir 35340, Turkey
2
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Ege University, Izmir 35340, Turkey
Presented at the 2nd International Cell Death Research Congress, Izmir, Turkey, 1–4 November 2018.
*
Author to whom correspondence should be addressed.
Published: 6 December 2018
PDF [1136 KB, uploaded 6 December 2018]

Abstract

Prostate cancer cells need androgens to grow and maintain like normal prostate cells, both utilize that Androgen Receptor (AR) function. Androgen receptor (AR) is expressed throughout the prostate cancer progression plays a critical role as a transcription factor in castration-dependent stages of disease. AR also interacts to many cellular proteins, including p53, to regulate apoptosis. Further, as the stabilization of p53 protein triggers apoptosis, p53 interacting small molecules such as Nutlin3a, are interpreted as cancer therapeutics. In this study, to find out how Nutlin3a-mediated p53 stabilization effect on AR signaling. Here, we investigated the dynamics of p53 binding to transcriptional targets of AR, and further investigated the variations of AR intracellular localization as well as transactivation in the presence of Nutlin3a. To do this, the changes in AR transactivation were investigated via luciferase reporter assay, which was performed by treating LNCaPs with different doses of Nutlin3a and resulted that transactivation was suppressed by Nutlin3a in a dose dependent manner. AR transactivation and sub-cellular localization were also studied by immunofluorescence assay and found that cytoplasmic-nuclear fractionation-coupled western blot analysis showed that Nutlin3a inhibits AR phosphorylation and nuclear translocation regardless of androgens.
Keywords: prostate cancer; AR; Nutlin3a; p53 prostate cancer; AR; Nutlin3a; p53
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Ozduman, G.; Butuner, B.D.; Korkmaz, K.S. Nutlin3a Contributes to the Cytoplasmic Retention of Androgen Receptor. Proceedings 2018, 2, 1580.

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