title: The PRKD1 promoter is a target of the KRas-NF-κB pathway in pancreatic cancer.
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.
authors.affiliation: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: Heike
authors.initials: H
authors.lastname: Döppler
authors.affiliation: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Panayiotou
authors.affiliation: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Reid
authors.affiliation: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: Willibroad
authors.initials: W
authors.lastname: Maimo
authors.affiliation: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: Ligia
authors.initials: L
authors.lastname: Bastea
authors.affiliation: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Storz
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000096:biosynthesis* / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C117307:KRAS protein, human; D016328:NF-kappa B; C089212:protein kinase D; D011493:Protein Kinase C; D016283:Proto-Oncogene Proteins p21(ras)