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BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Androgens | Research

NanoLuc Binary Technology as a methodological approach: an important new tool for studying the localization of androgen receptor and androgen receptor splice variant V7 homo and heterodimers

Authors: Juan Guzman, Katrin Weigelt, Angela Neumann, Philipp Tripal, Benjamin Schmid, Zoltán Winter, Ralph Palmisano, Zoran Culig, Marcus V. Cronauer, Paul Muschler, Bernd Wullich, Helge Taubert, Sven Wach

Published in: BMC Cancer | Issue 1/2024

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Abstract

Background

The androgen/androgen receptor (AR)-signaling axis plays a central role in prostate cancer (PCa). Upon androgen-binding the AR dimerizes with another AR, and translocates into the nucleus where the AR-dimer activates/inactivates androgen-dependent genes. Consequently, treatments for PCa are commonly based on androgen deprivation therapy (ADT). The clinical benefits of ADT are only transitory and most tumors develop mechanisms allowing the AR to bypass its need for physiological levels of circulating androgens. Clinical failure of ADT is often characterized by the synthesis of a constitutively active AR splice variant, termed AR-V7. AR-V7 mRNA expression is considered as a resistance mechanism following ADT. AR-V7 no longer needs androgenic stimuli for nuclear entry and/or dimerization.

Methods

Our goal was to mechanistically decipher the interaction between full-length AR (AR-FL) and AR-V7 in AR-null HEK-293 cells using the NanoLuc Binary Technology under androgen stimulation and deprivation conditions.

Results

Our data point toward a hypothesis that AR-FL/AR-FL homodimers form in the cytoplasm, whereas AR-V7/AR-V7 homodimers localize in the nucleus. However, after androgen stimulation, all the AR-FL/AR-FL, AR-FL/AR-V7 and AR-V7/AR-V7 dimers were localized in the nucleus.

Conclusions

We showed that AR-FL and AR-V7 form heterodimers that localize to the nucleus, whereas AR-V7/AR-V7 dimers were found to localize in the absence of androgens in the nucleus.
Appendix
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Metadata
Title
NanoLuc Binary Technology as a methodological approach: an important new tool for studying the localization of androgen receptor and androgen receptor splice variant V7 homo and heterodimers
Authors
Juan Guzman
Katrin Weigelt
Angela Neumann
Philipp Tripal
Benjamin Schmid
Zoltán Winter
Ralph Palmisano
Zoran Culig
Marcus V. Cronauer
Paul Muschler
Bernd Wullich
Helge Taubert
Sven Wach
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-12110-2

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