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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma.
Proc. Natl. Acad. Sci. U.S.A. 107, 13438-13443 (2010)
Pancreatic cancer is one of the most fatal malignancies lacking effective therapies. Notch signaling is a key regulator of cell fate specification and pancreatic cancer development; however, the role of individual Notch receptors and downstream signaling is largely unknown. Here, we show that Notch2 is predominantly expressed in ductal cells and pancreatic intraepithelial neoplasia (PanIN) lesions. Using genetically engineered mice, we demonstrate the effect of conditional Notch receptor ablation in KrasG12D-driven pancreatic carcinogenesis. Deficiency of Notch2 but not Notch1 stops PanIN progression, prolongs survival, and leads to a phenotypical switch toward anaplastic pancreatic cancer with epithelial-mesenchymal transition. By expression profiling, we identified increased Myc signaling regulated by Notch2 during tumor development, placing Notch2 as a central regulator of PanIN progression and malignant transformation. Our study supports the concept of distinctive roles of individual Notch receptors in cancer development.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Genetically engineered mice; K-Ras; Myc; Notch; Pancreatic cancer
ISSN (print) / ISBN
0027-8424
e-ISSN
1091-6490
Quellenangaben
Volume: 107,
Issue: 30,
Pages: 13438-13443
Publisher
National Academy of Sciences
Reviewing status
Peer reviewed
Institute(s)
Research Unit Gene Vector (AGV)