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

Guzman J, Weigelt K, Neumann AD, Tripal P, Schmid B, Winter Z, Palmisano R, Culig Z, Cronauer MV, Muschler P, Wullich B, Taubert H, Wach S (2024)

Publication Type: Journal article

Publication year: 2024

Journal

BMC Cancer BioMed Central

Book Volume: 24

Article Number: 346

Journal Issue: 1

DOI: 10.1186/s12885-024-12110-2

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.

Authors with CRIS profile

Juan Guzman Urologische Klinik Anna-Dorothea Neumann Medizinische Fakultät Philipp Tripal Optical Imaging Center Erlangen (OICE) Benjamin Schmid Optical Imaging Center Erlangen (OICE) Zoltan Winter Optical Imaging Center Erlangen (OICE) Ralf Palmisano FAU Optical Imaging Competence Center (FAU OICE) Bernd Wullich Lehrstuhl für Urologie Helge Taubert Professur für Molekulare Urologie Sven Wach Medizinische Fakultät

Involved external institutions

Medizinische Universität Innsbruck AT Austria (AT) Universitätsklinikum Bonn DE Germany (DE) Promega GmbH DE Germany (DE)

How to cite

APA:

Guzman, J., Weigelt, K., Neumann, A.-D., Tripal, P., Schmid, B., Winter, Z.,... Wach, S. (2024). 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. BMC Cancer, 24(1). https://doi.org/10.1186/s12885-024-12110-2

MLA:

Guzman, Juan, et al. "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." BMC Cancer 24.1 (2024).

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