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Endocrine

Published in:

01-11-2018 | Original Article

Androgenic modulation of AR-Vs

Authors: Ana Caroline Hillebrand, Lolita Schneider Pizzolato, Gisele Branchini, Ilma Simoni Brum

Published in: Endocrine | Issue 2/2018

Abstract

Purpose

The importance of androgen receptor variants (AR-Vs) is recognized in prostate cancer. AR-Vs have been the focus of many studies. Expression of AR-Vs has been proposed as a biomarker for resistance to androgen deprivation therapy for metastatic disease. Herein, we show dynamic changes in AR-Vs expression in response to androgen modulation.

Methods

The C4-2B cell line was exposed to low (10⁻¹³ M) and high (10⁻⁸ M) androgen (dihydrotestosterone, DHT) levels, with or without flutamide. mRNA and protein expression levels were assessed by qPCR and immunohistochemistry, respectively.

Results

We demonstrated that high levels of DHT downregulate AR-FL and AR-Vs. Even though AR-Vs did not present ligand-binding domain, thus were not capable of binding to DHT, they present dynamic changes under androgen treatment. Treatment with flutamide alone or in association with low levels of DHT stimulates growth of prostatic cells.

Conclusions

Importantly, we provide evidence that AR-Vs respond differently to androgenic modulation. These findings have implications for a better understanding of the role of AR-Vs in prostate carcinogenesis.

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Title: Androgenic modulation of AR-Vs
Authors: Ana Caroline Hillebrand
Lolita Schneider Pizzolato
Gisele Branchini
Ilma Simoni Brum
Publication date: 01-11-2018
Publisher: Springer US
Published in: Endocrine / Issue 2/2018
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-018-1682-5

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