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Functional roles of DTX3L and ARTD9 in prostate cancer


Bachmann, Samia Beatrice. Functional roles of DTX3L and ARTD9 in prostate cancer. 2014, University of Zurich, Vetsuisse Faculty.

Abstract

Prostate cancer (PCa) is one of the leading causes of cancer related mortality and morbidity in the aging male population. The B-lymphoma and BAL-associated protein (BBAP) and Deltex (DTX)-3-like E3 ubiquitin ligase (DTX3L), was originally identified as a binding partner of the B-aggressive lymphoma-1 protein and diphtheria-toxin-like ADP-ribosyltransferase-9 (BAL1/ARTD9). Here it is shown, that DTX3L and ARTD9 are both overexpressed in PCa cells. Together with ARTD8 (ADP-ribosyltransferase-8) they mediate proliferation, survival and chemo-resistance of PCa cells. The effects of DTX3L and ARTD9 are dependent on the signal transducer and activator of transcription factor 1 (STAT-1). STAT-1 is known as a tumor suppressor, activated by interferon γ (IFNγ). Its antitumor effects are mainly based on the activation of the transcription of the interferon responding factor 1 (IRF1). New reports showed that a constitutively activated STAT-1 leads to an IFNγ- and chemo-resistance of tumors and acts as an oncogene. Such a situation occurred also in the analyzed PCa cells. The presented study shows that DTX3L and ARTD9 repress the expression of IRF1. DTX3L also mediates migration of PCa cells in a STAT-1 and STAT-3-dependent manner. However, migration is not dependent on IFNy/IRF1. Together, this study suggests that the combined inhibition of STAT-1, ARTD8, ARTD9 and/or DTX3L could increase the efficacy of chemotherapy or radiation treatment in prostate cancer

Abstract

Prostate cancer (PCa) is one of the leading causes of cancer related mortality and morbidity in the aging male population. The B-lymphoma and BAL-associated protein (BBAP) and Deltex (DTX)-3-like E3 ubiquitin ligase (DTX3L), was originally identified as a binding partner of the B-aggressive lymphoma-1 protein and diphtheria-toxin-like ADP-ribosyltransferase-9 (BAL1/ARTD9). Here it is shown, that DTX3L and ARTD9 are both overexpressed in PCa cells. Together with ARTD8 (ADP-ribosyltransferase-8) they mediate proliferation, survival and chemo-resistance of PCa cells. The effects of DTX3L and ARTD9 are dependent on the signal transducer and activator of transcription factor 1 (STAT-1). STAT-1 is known as a tumor suppressor, activated by interferon γ (IFNγ). Its antitumor effects are mainly based on the activation of the transcription of the interferon responding factor 1 (IRF1). New reports showed that a constitutively activated STAT-1 leads to an IFNγ- and chemo-resistance of tumors and acts as an oncogene. Such a situation occurred also in the analyzed PCa cells. The presented study shows that DTX3L and ARTD9 repress the expression of IRF1. DTX3L also mediates migration of PCa cells in a STAT-1 and STAT-3-dependent manner. However, migration is not dependent on IFNy/IRF1. Together, this study suggests that the combined inhibition of STAT-1, ARTD8, ARTD9 and/or DTX3L could increase the efficacy of chemotherapy or radiation treatment in prostate cancer

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Additional indexing

Item Type:Dissertation (monographical)
Referees:Hottiger Michael O, Lutz Thomas
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Physiology
05 Vetsuisse Faculty > Department of Molecular Mechanisms of Disease
07 Faculty of Science > Department of Molecular Mechanisms of Disease

UZH Dissertations
Dewey Decimal Classification:570 Life sciences; biology
Uncontrolled Keywords:DTX3L, ARTD9, prostate cancer, proliferation, migration
Language:English
Place of Publication:Zürich
Date:2014
Deposited On:03 May 2019 11:17
Last Modified:18 Oct 2019 14:49
Number of Pages:50
OA Status:Green
Related URLs:https://www.recherche-portal.ch/primo-explore/fulldisplay?docid=ebi01_prod010161011&context=L&vid=ZAD&search_scope=default_scope&tab=default_tab&lang=de_DE (Library Catalogue)

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