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Biomedicines
Volume 10
Issue 2
10.3390/biomedicines10020473
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Article

Proteasome-Mediated Regulation of GATA2 Expression and Androgen Receptor Transcription in Benign Prostate Epithelial Cells

by
Waqas Azeem
1,2,3,*,†,
Jan Roger Olsen
1,
Margrete Reime Hellem
1,
Yaping Hua
1,
Kristo Marvyin
1,
Xisong Ke
1,
Anne Margrete Øyan
1,4 and
Karl-Henning Kalland
1,2,3,*,†
1
Department of Clinical Science, University of Bergen, 5021 Bergen, Norway
2
Centre for Cancer Biomarkers, University of Bergen, 5021 Bergen, Norway
3
Department of Microbiology, Haukeland University Hospital, 5021 Bergen, Norway
4
Department of Immunology and Transfusion Medicine, Haukeland University Hospital, 5021 Bergen, Norway
*
Authors to whom correspondence should be addressed.
†
Address: Laboratory Bld. 5th Floor, Helse Bergen, NO-5021 Bergen, Norway.
Biomedicines 2022, 10(2), 473; https://doi.org/10.3390/biomedicines10020473
Submission received: 12 January 2022 / Revised: 11 February 2022 / Accepted: 16 February 2022 / Published: 17 February 2022
(This article belongs to the Topic Cancer Biology and Therapy)
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Abstract

GATA2 has been shown to be an important transcription factor together with androgen receptor (AR) in prostate cancer cells. Less is known about GATA2 in benign prostate epithelial cells. We have investigated if GATA2 exogenous expression in prostate epithelial basal-like cells could induce AR transcription or luminal differentiation. Prostate epithelial basal-like (transit amplifying) cells were transduced with lentiviral vector expressing GATA2. Luminal differentiation markers were assessed by RT-qPCR, Western blot and global gene expression microarrays. We utilized our previously established AR and androgen-dependent fluorescence reporter assay to investigate AR activity at the single-cell level. Exogenous GATA2 protein was rapidly and proteasome-dependently degraded. GATA2 protein expression was rescued by the proteasome inhibitor MG132 and partly by mutating the target site of the E3 ligase FBXW7. Moreover, MG132-mediated proteasome inhibition induced AR mRNA and additional luminal marker gene transcription in the prostate transit amplifying cells. Different types of intrinsic mechanisms restricted GATA2 expression in the transit amplifying cells. The appearance of AR mRNA and additional luminal marker gene expression changes following proteasome inhibition suggests control of essential cofactor(s) of AR mRNA expression and luminal differentiation at this proteolytic level.
Keywords: prostate cell; luminal differentiation; androgen receptor; GATA2; proteasome; MG132 prostate cell; luminal differentiation; androgen receptor; GATA2; proteasome; MG132

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MDPI and ACS Style

Azeem, W.; Olsen, J.R.; Hellem, M.R.; Hua, Y.; Marvyin, K.; Ke, X.; Øyan, A.M.; Kalland, K.-H. Proteasome-Mediated Regulation of GATA2 Expression and Androgen Receptor Transcription in Benign Prostate Epithelial Cells. Biomedicines 2022, 10, 473. https://doi.org/10.3390/biomedicines10020473

AMA Style

Azeem W, Olsen JR, Hellem MR, Hua Y, Marvyin K, Ke X, Øyan AM, Kalland K-H. Proteasome-Mediated Regulation of GATA2 Expression and Androgen Receptor Transcription in Benign Prostate Epithelial Cells. Biomedicines. 2022; 10(2):473. https://doi.org/10.3390/biomedicines10020473

Chicago/Turabian Style

Azeem, Waqas, Jan Roger Olsen, Margrete Reime Hellem, Yaping Hua, Kristo Marvyin, Xisong Ke, Anne Margrete Øyan, and Karl-Henning Kalland. 2022. "Proteasome-Mediated Regulation of GATA2 Expression and Androgen Receptor Transcription in Benign Prostate Epithelial Cells" Biomedicines 10, no. 2: 473. https://doi.org/10.3390/biomedicines10020473

APA Style

Azeem, W., Olsen, J. R., Hellem, M. R., Hua, Y., Marvyin, K., Ke, X., Øyan, A. M., & Kalland, K.-H. (2022). Proteasome-Mediated Regulation of GATA2 Expression and Androgen Receptor Transcription in Benign Prostate Epithelial Cells. Biomedicines, 10(2), 473. https://doi.org/10.3390/biomedicines10020473

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