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Mazur, P.K.* ; Einwächter, H.* ; Lee, M.* ; Sipos, B.* ; Nakhai, H.* ; Rad, R.* ; Zimber-Strobl, U. ; Strobl, L.J. ; Radtke, F.* ; Klöppel, G.* ; Schmid, R.M.* ; Siveke, J.T.*

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)
DOI PMC
Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Genetically engineered mice; K-Ras; Myc; Notch; Pancreatic cancer
Sprache englisch
Veröffentlichungsjahr 2010
HGF-Berichtsjahr 2010
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Zeitschrift Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Band: 107, Heft: 30, Seiten: 13438-13443 Artikelnummer: , Supplement: ,
Verlag National Academy of Sciences
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Gene Vector (AGV)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501500-003
PubMed ID 20624967
DOI 10.1073/pnas.1002423107
Scopus ID 77955827414
Erfassungsdatum 2010-11-16
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