Cited by 643Pancreatic and Hepatic Oncology ResearchDevelopmental Biology and Gene RegulationPancreatic function and diabetes

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Notch mediates TGFα-induced changes in epithelial differentiation during pancreatic tumorigenesis

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Miyamoto, Yoshiharu, Maitra, Anirban, Ghosh, Bidyut, Zechner, Ulrich, Argani, Pedram, Iacobuzio-Donahue, Christine A., Sriuranpong, Virote, Iso, Tatsuya, Meszoely, Ingrid M., Wolfe, Michael S., Hruban, Ralph H., Ball, Douglas W., Schmid, Roland M., Leach, Steven D.·2003·Cancer Cell

DOI 10.1016/s1535-6108(03)00140-5

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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 TGF alpha-induced changes in epithelial differentiation. These findings suggest that Notch mediates the tumor-initiating effects of TG alpha by expanding a population of undifferentiated precursor cells.

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Gao, J., Sarkar, F. H., Miele, L., & Wang, Z. P. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-408103-1.00004-2
Importance de la voie Notch dans la dysfonction endothéliale en transplantation : régulation et fonctions des récepteurs Notch2 et Notch4
Quillard, T. (2008) · OpenGrey (Institut de l'Information Scientifique et Technique)
Expression of CD133 and Extracellular Matrix Molecules in Malignant Brain Tumors
Yoshida, S., & Koike, T. (2011) · Neuroscience & Medicine · doi:10.4236/nm.2011.24052
Can Findings of DMBA-Induced Pancreatic Cancer Model in Mice Be Applied to Studies of Human Pancreatic Carcinogenesis?
Satoh, K., Kimura, K., Kanno, A., Hamada, S., Hirota, M., & Shimosegawa, T. (2009) · Pancreas · doi:10.1097/01.mpa.0000357026.62050.25
Notch Signaling in Human Neuroblastoma Cells
Stockhausen, M. (2005) · Lund University Publications (Lund University)
LG-04 * NOTCH SIGNALING ACTIVATION IN PEDIATRIC LOW-GRADE ASTROCYTOMA
Brandt, W. D., Schreck, K. C., Bar, E. E., Taylor, I., Marchionni, L., Raabe, E. H., Eberhart, C. G., & Rodríguez, F. J. (2015) · Neuro-Oncology · doi:10.1093/neuonc/nov061.73
Med29 Possesses a Complex Role in Pancreatic Cancer
Kuuselo, R. (2010) · Tampere University Institutional Repository (Tampere University)
Expressionsanalyse von Notch 1, Notch 2 und Cyclin D1 in Gliomen
Direktor, Ä., & Meyermann, R. (2011)

Authors: Miyamoto, Y., Maitra, A., Ghosh, B., Zechner, U., Argani, P., Iacobuzio-Donahue, C. A., Sriuranpong, V., Iso, T., Meszoely, I. M., Wolfe, M. S., Hruban, R. H., Ball, D. W., Schmid, R. M., & Leach, S. D.
Affiliations: Johns Hopkins University (US)
Universität Ulm (DE)
Gunma University (JP)
Fox Chase Cancer Center (US)
Harvard University (US)
Corresponding author: Leach, Steven D.
ORCID: Maitra, Anirban
Zechner, Ulrich
Argani, Pedram
Sriuranpong, Virote
Iso, Tatsuya
Meszoely, Ingrid M.
Wolfe, Michael S.
Hruban, Ralph H.
Schmid, Roland M.
Leach, Steven D.
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2003-06
Volume: 3
Issue: 6
Pages: 565-576
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/s1535-6108(03)00140-5
OpenAlex: W2148054025
Cited by: 643
References: 69
Citations by year: 2026: 3 · 2025: 5 · 2024: 7 · 2023: 11 · 2022: 17 · 2021: 19 · 2020: 15 · 2019: 15 · 2018: 33 · 2017: 27 · 2016: 26 · 2015: 27 · 2014: 34 · 2013: 36 · 2012: 37
FWCI: 15.11
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 3699 d)
Locations: Cancer Cell (publishedVersion)
PubMed (publishedVersion)
mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
Funders: National Institutes of Health
National Cancer Institute (CA 70244, F32 CA 76698, R01CA070244, F32CA076698, P50CA062924, CA 62924)
National Institute of Diabetes and Digestive and Kidney Diseases (DK56211, R01DK056211, DK61215, R01DK061215)
National Institute of Neurological Disorders and Stroke (R01NS041355, NS41355)
Topics: Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Keywords: Notch signaling, transforming growth factor-alpha, pancreatic cancer, pancreatic carcinogenesis, epithelial differentiation, pancreatic cancer precursors, EGF receptor activation, tumor initiation, exocrine pancreas
MeSH terms: Animals, Cell Differentiation, Cells, Cultured, Epithelial Cells, Humans, Intermediate Filament Proteins, Membrane Proteins, Mice, Transgenic, Neoplasm Invasiveness, Nerve Tissue Proteins, Pancreatic Neoplasms, Signal Transduction, Biomarkers, Up-Regulation, Transforming Growth Factor alpha, Disease Progression, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Carcinoma, Ductal, Mice, Receptors, Notch, Nestin, ErbB Receptors

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Notch mediates TGFα-induced changes in epithelial differentiation during pancreatic tumorigenesis

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