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PRSS1 mutation: a possible pathomechanism of pancreatic carcinogenesis and pancreatic cancer
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744682/ https://www.ncbi.nlm.nih.gov/pubmed/31521106 http://dx.doi.org/10.1186/s10020-019-0111-4 |
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author | Liu, Qicai Guo, Ling Zhang, Sheng Wang, Jingwen Lin, Xinhua Gao, Feng |
author_facet | Liu, Qicai Guo, Ling Zhang, Sheng Wang, Jingwen Lin, Xinhua Gao, Feng |
author_sort | Liu, Qicai |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s10020-019-0111-4. |
format | Online Article Text |
id | pubmed-6744682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-67446822019-09-18 PRSS1 mutation: a possible pathomechanism of pancreatic carcinogenesis and pancreatic cancer Liu, Qicai Guo, Ling Zhang, Sheng Wang, Jingwen Lin, Xinhua Gao, Feng Mol Med Research Article 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. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s10020-019-0111-4. BioMed Central 2019-09-14 /pmc/articles/PMC6744682/ /pubmed/31521106 http://dx.doi.org/10.1186/s10020-019-0111-4 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Liu, Qicai Guo, Ling Zhang, Sheng Wang, Jingwen Lin, Xinhua Gao, Feng PRSS1 mutation: a possible pathomechanism of pancreatic carcinogenesis and pancreatic cancer |
title | PRSS1 mutation: a possible pathomechanism of pancreatic carcinogenesis and pancreatic cancer |
title_full | PRSS1 mutation: a possible pathomechanism of pancreatic carcinogenesis and pancreatic cancer |
title_fullStr | PRSS1 mutation: a possible pathomechanism of pancreatic carcinogenesis and pancreatic cancer |
title_full_unstemmed | PRSS1 mutation: a possible pathomechanism of pancreatic carcinogenesis and pancreatic cancer |
title_short | PRSS1 mutation: a possible pathomechanism of pancreatic carcinogenesis and pancreatic cancer |
title_sort | prss1 mutation: a possible pathomechanism of pancreatic carcinogenesis and pancreatic cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744682/ https://www.ncbi.nlm.nih.gov/pubmed/31521106 http://dx.doi.org/10.1186/s10020-019-0111-4 |
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