Cited by 2,471Pancreatic and Hepatic Oncology ResearchCancer Genomics and DiagnosticsPancreatic function and diabetes

The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.

Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse

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Abstract

To evaluate the role of oncogenic RAS mutations in pancreatic tumorigenesis, we directed endogenous expression of KRAS(G12D) to progenitor cells of the mouse pancreas. We find that physiological levels of Kras(G12D) induce ductal lesions that recapitulate the full spectrum of human pancreatic intraepithelial neoplasias (PanINs), putative precursors to invasive pancreatic cancer. The PanINs are highly proliferative, show evidence of histological progression, and activate signaling pathways normally quiescent in ductal epithelium, suggesting potential therapeutic and chemopreventive targets for the cognate human condition. At low frequency, these lesions also progress spontaneously to invasive and metastatic adenocarcinomas, establishing PanINs as definitive precursors to the invasive disease. Finally, mice with PanINs have an identifiable serum proteomic signature, suggesting a means of detecting the preinvasive state in patients.

Overview

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Crossref · 10.1016/s1535-6108(03)00309-x

Cites

62 of 62 references verified0 citation errors · 0 not checkable

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Research works printed but not linked: 1

  1. Kern, 2001, A white paper, Cancer Res., 61, 4923

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Metadata

Authors
Hingorani, S. R., Petricoin, E. F., Maitra, A., Rajapakse, V., King, C., Jacobetz, M. A., Ross, S., Conrads, T. P., Veenstra, T. D., Hitt, B. A., Kawaguchi, Y., Johann, D., Liotta, L. A., Crawford, H. C., Putt, M. E., Jacks, T., Wright, C. V. E., Hruban, R. H., Lowy, A. M., & Tuveson, D. A.
Affiliations
  • Abramson Cancer Center (US)
  • Center for Biologics Evaluation and Research (US)
  • Johns Hopkins University (US)
  • National Cancer Institute (US)
  • Vanderbilt University (US)
  • State University of New York (US)
  • University of Pennsylvania (US)
  • Howard Hughes Medical Institute (US)
  • University of Cincinnati (US)
Corresponding author
Tuveson, David A.
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2003-12
Volume
4
Issue
6
Pages
437-450
ISSN
1535-6108 (ISSN-L)
OpenAlex
W2066135299
Cited by
2,471
References
62
Citations by year
2026: 75 · 2025: 112 · 2024: 106 · 2023: 137 · 2022: 132 · 2021: 141 · 2020: 156 · 2019: 143 · 2018: 145 · 2017: 148 · 2016: 142 · 2015: 140 · 2014: 145 · 2013: 138 · 2012: 102
FWCI
18.85
Type
journal article
Language
en
Open access
Locations
  • Cancer Cell (publishedVersion)
  • PubMed (publishedVersion)
  • DigitalCommons-Cedarville (Cedarville University) (submittedVersion)
Funders
  • National Cancer Institute (R25-CA87812, P50CA-62924, R25CA087812, P50CA062924)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK050306)
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Keywords
pancreatic ductal adenocarcinoma, pancreatic intraepithelial neoplasia, KRAS G12D, oncogenic Ras mutations, pancreatic progenitor cells, pancreatic carcinogenesis, metastatic adenocarcinoma, early cancer detection, chemoprevention, mouse model
MeSH terms
Transcription Factor HES-1, Animals, Humans, Immunohistochemistry, Isoenzymes, Membrane Proteins, Mutation, Neoplasm Metastasis, Neoplasm Staging, Pancreas, Pancreatic Neoplasms, Prostaglandin-Endoperoxide Synthases, Genes, ras, Homeodomain Proteins, Matrix Metalloproteinase 7, Carcinoma, Pancreatic Ductal, Mice, Cyclooxygenase 2, Basic Helix-Loop-Helix Proteins

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