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The PRKD1 promoter is a target of the KRas-NF-κB pathway in pancreatic cancer

Increased expression of PRKD1 and its gene product protein kinase D1 (PKD1) are linked to oncogenic signaling in pancreatic ductal adenocarcinoma, but a direct functional relationship to oncogenic KRas has not been established so far. We here describe the PRKD1 gene promoter as a target for oncogeni...

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Autores principales: Döppler, Heike, Panayiotou, Richard, Reid, Elizabeth M., Maimo, Willibroad, Bastea, Ligia, Storz, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030668/
https://www.ncbi.nlm.nih.gov/pubmed/27649783
http://dx.doi.org/10.1038/srep33758
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author Döppler, Heike
Panayiotou, Richard
Reid, Elizabeth M.
Maimo, Willibroad
Bastea, Ligia
Storz, Peter
author_facet Döppler, Heike
Panayiotou, Richard
Reid, Elizabeth M.
Maimo, Willibroad
Bastea, Ligia
Storz, Peter
author_sort Döppler, Heike
collection PubMed
description Increased expression of PRKD1 and its gene product protein kinase D1 (PKD1) are linked to oncogenic signaling in pancreatic ductal adenocarcinoma, but a direct functional relationship to oncogenic KRas has not been established so far. We here describe the PRKD1 gene promoter as a target for oncogenic KRas signaling. We demonstrate that KRas-induced activation of the canonical NF-κB pathway is one mechanism of how PRKD1 expression is increased and identify the binding sites for NF-κB in the PRKD1 promoter. Altogether, these results describe a novel mechanism governing PRKD1 gene expression in PDA and provide a functional link between oncogenic KRas, NF-κB and expression of PRKD1.
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spelling pubmed-50306682016-09-26 The PRKD1 promoter is a target of the KRas-NF-κB pathway in pancreatic cancer Döppler, Heike Panayiotou, Richard Reid, Elizabeth M. Maimo, Willibroad Bastea, Ligia Storz, Peter Sci Rep Article Increased expression of PRKD1 and its gene product protein kinase D1 (PKD1) are linked to oncogenic signaling in pancreatic ductal adenocarcinoma, but a direct functional relationship to oncogenic KRas has not been established so far. We here describe the PRKD1 gene promoter as a target for oncogenic KRas signaling. We demonstrate that KRas-induced activation of the canonical NF-κB pathway is one mechanism of how PRKD1 expression is increased and identify the binding sites for NF-κB in the PRKD1 promoter. Altogether, these results describe a novel mechanism governing PRKD1 gene expression in PDA and provide a functional link between oncogenic KRas, NF-κB and expression of PRKD1. Nature Publishing Group 2016-09-21 /pmc/articles/PMC5030668/ /pubmed/27649783 http://dx.doi.org/10.1038/srep33758 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Döppler, Heike
Panayiotou, Richard
Reid, Elizabeth M.
Maimo, Willibroad
Bastea, Ligia
Storz, Peter
The PRKD1 promoter is a target of the KRas-NF-κB pathway in pancreatic cancer
title The PRKD1 promoter is a target of the KRas-NF-κB pathway in pancreatic cancer
title_full The PRKD1 promoter is a target of the KRas-NF-κB pathway in pancreatic cancer
title_fullStr The PRKD1 promoter is a target of the KRas-NF-κB pathway in pancreatic cancer
title_full_unstemmed The PRKD1 promoter is a target of the KRas-NF-κB pathway in pancreatic cancer
title_short The PRKD1 promoter is a target of the KRas-NF-κB pathway in pancreatic cancer
title_sort prkd1 promoter is a target of the kras-nf-κb pathway in pancreatic cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030668/
https://www.ncbi.nlm.nih.gov/pubmed/27649783
http://dx.doi.org/10.1038/srep33758
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