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

PRKD1 启动子是胰腺癌中 KRas-NF-κB 通路的靶点

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作者:Heike Döppler, Richard Panayiotou, Elizabeth M Reid, Willibroad Maimo, Ligia Bastea, Peter Storz

Abstract

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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