作者
Carla E Cano, Tewfik Hamidi, Maria Noé Garcia, Daniel Grasso, Céline Loncle, Stéphane Garcia, Ezequiel Calvo, Gwen Lomberk, Nelson Dusetti, Laurent Bartholin, Raul Urrutia, Juan L Iovanna
发表日期
2014/6/1
期刊
Gut
卷号
63
期号
6
页码范围
984-995
出版商
BMJ Publishing Group
简介
Background
Nuclear protein 1 (Nupr1) is a major factor in the cell stress response required for KrasG12D-driven formation of pancreatic intraepithelial neoplastic lesions (PanINs). We evaluated the relevance of Nupr1 in the development of pancreatic cancer.
Methods
We investigated the role of Nupr1 in pancreatic ductal adenocarcinoma (PDAC) progression beyond PanINs in Pdx1-cre;LSL-KrasG12D;Ink4a/Arffl/fl(KIC) mice.
Results
Even in the context of the second tumorigenic hit of Ink4a/Arf deletion, Nupr1 deficiency led to suppression of malignant transformation involving caspase 3 activation in premalignant cells of KIC pancreas. Only half of Nupr1-deficient;KIC mice achieved PDAC development, and incident cases survived longer than Nupr1wt;KIC mice. This was associated with the development of well-differentiated PDACs in Nupr1-deficient;KIC mice, which displayed enrichment of genes characteristic …
学术搜索中的文章
CE Cano, T Hamidi, MN Garcia, D Grasso, C Loncle… - Gut, 2014