Open AccessThe PRKD1 promoter is a target of the KRas-NF-κB pathway in pancreatic cancer
Author(s) -
Heike Döppler,
Richard Panayiotou,
Elizabeth M. Reid,
Willibroad Maimo,
Ligia I. Bastea,
Peter Störz
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep33758
Subject(s) - kras , cancer research , pancreatic cancer , gene , mechanism (biology) , signal transduction , nf κb , biology , gene expression , cancer , mutation , genetics , philosophy , epistemology
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 .