Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice
Open accessAbstract
Pancreatic ductal adenocarcinoma (PDA), one of the deadliest human cancers, often involves somatic activation of K-Ras oncogenes. We report that selective expression of an endogenous K-Ras(G12V) oncogene in embryonic cells of acinar/centroacinar lineage results in pancreatic intraepithelial neoplasias (PanINs) and invasive PDA, suggesting that PDA originates by differentiation of acinar/centroacinar cells or their precursors into ductal-like cells. Surprisingly, adult mice become refractory to K-Ras(G12V)-induced PanINs and PDA. However, if these mice are challenged with a mild form of chronic pancreatitis, they develop the full spectrum of PanINs and invasive PDA. These observations suggest that, during adulthood, PDA stems from a combination of genetic (e.g., somatic K-Ras mutations) and nongenetic (e.g., tissue damage) events.
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Activation of the LSL-Kras allele using elastase-driven Cre in acinar cells results in PanIN development.
“On the other hand, activation of the LSL-Kras allele using elastase-driven Cre, which is expressed in acinar cells, results in PanIN development (80).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [80]
Tumor development in adult mice can be greatly accelerated by chemically induced pancreatitis.
“Tumor development in adult mice, however, can be greatly accelerated by chemically induced pancreatitis.”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [80]
Inflammatory signaling is likely to play a critical role in pancreatic cancer development.
“Thus, inflammatory signaling is likely to play a critical role in pancreatic cancer development (80, 81).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [80]
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Self-citation
- Authors
- Guerra, C., Schuhmacher, A. J., Cañamero, M., Grippo, P. J., Verdaguer, L., Pérez-Gallego, L., Dubus, P., Sandgren, E. P., & Barbacid, M.
- Affiliations
- Spanish National Cancer Research Centre (ES)
- Northwestern University (US)
- Université de Bordeaux (FR)
- University of Wisconsin–Madison (US)
- Corresponding author
- Guerra, Carmen
- Barbacid, Mariano
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 11
- Issue
- 3
- Pages
- 291-302
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2056646351
- Cited by
- 1,224
- References
- 45
- Citations by year
- 2026: 51 · 2025: 46 · 2024: 55 · 2023: 71 · 2022: 56 · 2021: 95 · 2020: 81 · 2019: 73 · 2018: 61 · 2017: 65 · 2016: 75 · 2015: 69 · 2014: 89 · 2013: 69 · 2012: 67
- FWCI
- 24.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission (QLG2-CT-2002-00930)
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- pancreatic ductal adenocarcinoma, chronic pancreatitis, KRAS G12V, pancreatic intraepithelial neoplasia, tumor initiation, tissue damage, mouse model, somatic mutations, cancer stem cells
- MeSH terms
- Animals, Ceruletide, Carcinoma in Situ, Cell Transformation, Neoplastic, Doxycycline, Liver Neoplasms, Lung Neoplasms, Mice, Mutant Strains, Mutation, Neoplasm Invasiveness, Pancreas, Pancreatic Neoplasms, Genes, ras, Signal Transduction, Cell Lineage, Carcinoma, Pancreatic Ductal, Pancreatitis, Chronic, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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