Molecular medicine (Cambridge, Mass.) · 2019
PRSS1 mutation: a possible pathomechanism of pancreatic carcinogenesis and pancreatic cancer.
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Liu Qicai, Guo Ling, Zhang Sheng, Wang Jingwen, Lin Xinhua, Gao Feng
Аннотация
BACKGROUND: Previous studies revealed somatic mutations of the cationic trypsinogen gene (PRSS1) in patients with chronic pancreatitis and pancreatic cancer. However, whether PRSS1 mutations trigger pancreatic cancer and/or promote malignant proliferation and metastasis in pancreatic cancer remains largely unclear, as well as the potential underlying mechanisms.
METHODS: In the present study, whole-exome sequencing was applied for screening, and the R116C mutation was validated by Sanger sequencing. Phosphorylation antibody array, RNA-Seq, and RT-qPCR were adopted to screen and validate that R116C mutation promoted pancreatic cancer progression via the JAK1-STAT5 pathway.
RESULTS: It showed that migration and invasion were significantly increased in R116C-bearing PANC-1 cells compared with wild type counterparts. In a transgenic mouse model of iZEG-PRSS1_R116C, primary pancreatic intraepithelial neoplasia (PanINs) was observed in the pancreatic duct.
CONCLUSIONS: These findings suggested a novel pathway mediating pancreatic cancer development, with PRSS1 mutation and overexpression playing an "inside job" role in pancreatic carcinogenesis and tumor development.
METHODS: In the present study, whole-exome sequencing was applied for screening, and the R116C mutation was validated by Sanger sequencing. Phosphorylation antibody array, RNA-Seq, and RT-qPCR were adopted to screen and validate that R116C mutation promoted pancreatic cancer progression via the JAK1-STAT5 pathway.
RESULTS: It showed that migration and invasion were significantly increased in R116C-bearing PANC-1 cells compared with wild type counterparts. In a transgenic mouse model of iZEG-PRSS1_R116C, primary pancreatic intraepithelial neoplasia (PanINs) was observed in the pancreatic duct.
CONCLUSIONS: These findings suggested a novel pathway mediating pancreatic cancer development, with PRSS1 mutation and overexpression playing an "inside job" role in pancreatic carcinogenesis and tumor development.