@article{620ea2f05a5641ae9ea52196acf4b510,
title = "Notch mediates TGFα-induced changes in epithelial differentiation during pancreatic tumorigenesis",
abstract = "Notch signaling regulates cell fate decisions in a wide variety of adult and embryonic tissues. Here we show that Notch pathway components and Notch target genes are upregulated in invasive pancreatic cancer, as well as in pancreatic cancer precursors from both mouse and human. In mouse pancreas, ectopic Notch activation results in accumulation of nestin-positive precursor cells and expansion of metaplastic ductal epithelium, previously identified as a precursor lesion for pancreatic cancer. Notch is also activated as a direct consequence of EGF receptor activation in exocrine pancreas and is required for TGFα-induced changes in epithelial differentiation. These findings suggest that Notch mediates the tumor-initiating effects of TGFα by expanding a population of undifferentiated precursor cells.",
author = "Yoshiharu Miyamoto and Anirban Maitra and Bidyut Ghosh and Ulrich Zechner and Pedram Argani and Iacobuzio-Donahue, {Christine A.} and Virote Sriuranpong and Tatsuya Iso and Meszoely, {Ingrid M.} and Wolfe, {Michael S.} and Hruban, {Ralph H.} and Ball, {Douglas W.} and Schmid, {Roland M.} and Leach, {Steven D.}",
note = "Funding Information: The authors wish to thank Dr. Kazufumi Suzuki for production of adenoviral vectors, Dr. Manju Kaushal for assistance with immunohistochemistry, and Ayman Rahman for performing in situ hybridization. The authors gratefully acknowledge Dr. Eric Sandgren for provision of transgenic mouse lines, Dr. Tetsuo Sudo and Dr. Ron McKay for generously providing anti-Hes1 and anti-nestin antisera, and Drs. Robert Coffey, Jeff Franklin, Scott Kern, Stephen Baylin, and Neil Watkins for helpful discussions. This study was supported by National Institutes of Health (NIH) grants DK-61215 and DK-56211 (to S.D.L.), CA-70244 (to D.W.B.), NS-41355 (to M.S.W.), F32 CA-76698 (to I.M.M.), by NIH Specialized Program of Research Excellence (SPORE grant) CA62924, and by a grant from the Lustgarten Foundation for Pancreatic Cancer Research (to S.D.L.). S.D.L. is also supported by the Paul K. Neumann Professorship in Pancreatic Cancer at Johns Hopkins University.",
year = "2003",
month = jun,
day = "1",
doi = "10.1016/S1535-6108(03)00140-5",
language = "English (US)",
volume = "3",
pages = "565--576",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",
}