Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL 32224, USA.
Sci Rep. 2016 Sep 21;6:33758. doi: 10.1038/srep33758.
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.
PRKD1 及其基因产物蛋白激酶 D1（PKD1）的表达增加与胰腺导管腺癌中的致癌信号有关，但迄今为止尚未建立与致癌 KRas 的直接功能关系。我们在这里将 PRKD1 基因启动子描述为致癌 KRas 信号的靶标。我们证明 KRas 诱导的经典 NF-κB 途径的激活是 PRKD1 表达增加的一种机制，并确定了 PRKD1 启动子中 NF-κB 的结合位点。总的来说，这些结果描述了一种新的机制，该机制控制着 PDA 中 PRKD1 基因的表达，并为致癌 KRas、NF-κB 和 PRKD1 表达之间提供了功能联系。
