PRSS1 Mutations Affect Pancreatic Ductal Adenocarcinoma Radiosensitivity via AKT and Extracellular Regulated Protein Kinases Pathways

Abstract

Radioresistance is the leading cause of failed radiation therapy for pancreatic ductal cancer (PDAC). The relevance of the cationic trypsinogen gene (PRSS1) in PDAC radioresistance is unknown, despite its association with tumor responses to therapy in numerous malignancies. Here we established two PRSS1 point mutation PDAC cell lines: c. 338 T > G and c.410 C > T. Compared to their parental cells, elevated AKT and ERK phosphorylation concentrations were observed in Panc-1 and MIA PaCa-2 c. 338 T > G and c.410 C > T cells with point mutations. The PRSS1 mutation restored the sensitivity of radioresistant cells to radiation through increased ionizing radiation-induced apoptosis by down regulating p-AKT and p-ERK. Based on these results, we hypothesized that a PRSS1 mutation in PDAC increased cell radiosensitivity by decreasing p-AKT and p-ERK. Our findings provide a molecular basis for optimizing radiation in patients with PDAC.