Upregulation of PRKD1 gene expression by activated K‐ras in pancreatic cancer cells (609.20)

Abstract

Summary Activating mutations of the K‐ras proto‐oncogene are detected in over 95% of pancreatic adenocarcinoma (PDA) and its precursor lesions. One mechanism by which activated K‐ras can drive the development of PDA is activation of the transcription factor nuclear factor κ‐B (NF‐κB), which has been shown to regulate genes involved in all aspects of tumor formation and progression. We here describe the PRKD1 gene promoter as a target for K‐ras‐NF‐κB signaling. We identify the binding sites for NF‐κB in the PRKD1 promoter and show that K‐ras‐driven upregulation of expression of PRKD1 and its gene product protein kinase D1 (PKD1) is linked to increased cell survival and oncogenic signaling in PDA.Conclusion Our data provide a functional link between oncogenic K‐ras, NF‐κB and PKD1, a targetable kinase in this cancer.Grant Funding Source: Supported by the NCI R01 grant CA140182