Increased Expression of AKT3 in Neuroendocrine Differentiated Prostate Cancer Cells Alters the Response Towards Anti-Androgen Treatment
Patients with advanced prostate carcinoma are often treated with an androgen deprivation therapy but long-term treatment can result in a metastatic castration-resistant prostate cancer. This is a more aggressive, untreatable tumor recurrence often containing areas of neuroendocrine differentiated pr...
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doaj-30afa0f11c7344aaa9483227a636068b2021-02-03T00:03:25ZengMDPI AGCancers2072-66942021-02-011357857810.3390/cancers13030578Increased Expression of AKT3 in Neuroendocrine Differentiated Prostate Cancer Cells Alters the Response Towards Anti-Androgen TreatmentMarc Wiesehöfer0Elena Dilara Czyrnik1Martin Spahn2Saskia Ting3Henning Reis4Jaroslaw Thomas Dankert5Gunther Wennemuth6Department of Anatomy, University Duisburg-Essen, D-45147 Essen, GermanyDepartment of Anatomy, University Duisburg-Essen, D-45147 Essen, GermanyDepartment of Urology, Lindenhofspital Bern, CHE-3012 Bern, SwitzerlandInstitute of Pathology, University Duisburg-Essen, D-45147 Essen, GermanyInstitute of Pathology, University Duisburg-Essen, D-45147 Essen, GermanyDepartment of Anatomy, University Duisburg-Essen, D-45147 Essen, GermanyDepartment of Anatomy, University Duisburg-Essen, D-45147 Essen, GermanyPatients with advanced prostate carcinoma are often treated with an androgen deprivation therapy but long-term treatment can result in a metastatic castration-resistant prostate cancer. This is a more aggressive, untreatable tumor recurrence often containing areas of neuroendocrine differentiated prostate cancer cells. Using an in vitro model of NE-like cancer cells, it could previously be shown that neuroendocrine differentiation of LNCaP cells leads to a strong deregulation of mRNA and miRNA expression. We observe elevated RNA and protein levels of AKT Serine/Threonine Kinase 3 (AKT3) in neuroendocrine-like LNCaP cells. We used prostate resections from patients with neuroendocrine prostate cancer to validate these results and detect a co-localization of neuroendocrine marker genes with AKT3. Analysis of downstream target genes FOXO3A and GSK3 strengthens the assumption AKT3 may play a role in neuroendocrine differentiation. Overexpression of AKT3 shows an increased survival rate of LNCaP cells after apoptosis induction, which in turn reflects the significance in vivo or for treatment. Furthermore, miR-17, −20b and −106b, which are decreased in neuroendocrine-like LNCaP cells, negatively regulate AKT3 biosynthesis. Our findings demonstrate AKT3 as a potential therapeutic target and diagnostic tool in advanced neuroendocrine prostate cancer and a new mRNA–miRNA interaction with a potential role in neuroendocrine differentiation of prostate cancer.https://www.mdpi.com/2072-6694/13/3/578prostate cancerneuroendocrine differentiationNE-like LNCaP cellsAKT3miR-17 family |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marc Wiesehöfer Elena Dilara Czyrnik Martin Spahn Saskia Ting Henning Reis Jaroslaw Thomas Dankert Gunther Wennemuth |
spellingShingle |
Marc Wiesehöfer Elena Dilara Czyrnik Martin Spahn Saskia Ting Henning Reis Jaroslaw Thomas Dankert Gunther Wennemuth Increased Expression of AKT3 in Neuroendocrine Differentiated Prostate Cancer Cells Alters the Response Towards Anti-Androgen Treatment Cancers prostate cancer neuroendocrine differentiation NE-like LNCaP cells AKT3 miR-17 family |
author_facet |
Marc Wiesehöfer Elena Dilara Czyrnik Martin Spahn Saskia Ting Henning Reis Jaroslaw Thomas Dankert Gunther Wennemuth |
author_sort |
Marc Wiesehöfer |
title |
Increased Expression of AKT3 in Neuroendocrine Differentiated Prostate Cancer Cells Alters the Response Towards Anti-Androgen Treatment |
title_short |
Increased Expression of AKT3 in Neuroendocrine Differentiated Prostate Cancer Cells Alters the Response Towards Anti-Androgen Treatment |
title_full |
Increased Expression of AKT3 in Neuroendocrine Differentiated Prostate Cancer Cells Alters the Response Towards Anti-Androgen Treatment |
title_fullStr |
Increased Expression of AKT3 in Neuroendocrine Differentiated Prostate Cancer Cells Alters the Response Towards Anti-Androgen Treatment |
title_full_unstemmed |
Increased Expression of AKT3 in Neuroendocrine Differentiated Prostate Cancer Cells Alters the Response Towards Anti-Androgen Treatment |
title_sort |
increased expression of akt3 in neuroendocrine differentiated prostate cancer cells alters the response towards anti-androgen treatment |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-02-01 |
description |
Patients with advanced prostate carcinoma are often treated with an androgen deprivation therapy but long-term treatment can result in a metastatic castration-resistant prostate cancer. This is a more aggressive, untreatable tumor recurrence often containing areas of neuroendocrine differentiated prostate cancer cells. Using an in vitro model of NE-like cancer cells, it could previously be shown that neuroendocrine differentiation of LNCaP cells leads to a strong deregulation of mRNA and miRNA expression. We observe elevated RNA and protein levels of AKT Serine/Threonine Kinase 3 (AKT3) in neuroendocrine-like LNCaP cells. We used prostate resections from patients with neuroendocrine prostate cancer to validate these results and detect a co-localization of neuroendocrine marker genes with AKT3. Analysis of downstream target genes FOXO3A and GSK3 strengthens the assumption AKT3 may play a role in neuroendocrine differentiation. Overexpression of AKT3 shows an increased survival rate of LNCaP cells after apoptosis induction, which in turn reflects the significance in vivo or for treatment. Furthermore, miR-17, −20b and −106b, which are decreased in neuroendocrine-like LNCaP cells, negatively regulate AKT3 biosynthesis. Our findings demonstrate AKT3 as a potential therapeutic target and diagnostic tool in advanced neuroendocrine prostate cancer and a new mRNA–miRNA interaction with a potential role in neuroendocrine differentiation of prostate cancer. |
topic |
prostate cancer neuroendocrine differentiation NE-like LNCaP cells AKT3 miR-17 family |
url |
https://www.mdpi.com/2072-6694/13/3/578 |
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