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
Open accessAbstract
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
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Expression of mutant Kras alone from embryonic pancreatic cells results in PanIN with histological and molecular features that resemble PanIN in human PDACs (72).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [72]
In the citing paper
“conditional expression of oncogenic mutant Kras in the pancreas, using Cre-recombinase driven by pancreatic transcription factor promoters activated during embryonic development, leads to development of murine PanIN lesions histologically reminiscent of human disease28.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [28]
Citations
Cites
A genetic model for colorectal tumorigenesis
Fearon, E. R., & Vogelstein, B. (1990) · Cell · doi:10.1016/0092-8674(90)90186-i · Cited by 12,132
Stem cells, cancer, and cancer stem cells
Reya, T., Morrison, S. J., Clarke, M. F., & Weissman, I. L. (2001) · Nature · doi:10.1038/35102167 · Cited by 9,738
Spencer, P. M., Cameron, J. L., & Lin, L. (2000) · Cited by 7,202
Notch Signaling: Cell Fate Control and Signal Integration in Development
Artavanis-Tsakonas, S., Rand, M. D., & Lake, R. J. (1999) · Science · doi:10.1126/science.284.5415.770 · Cited by 5,909
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218 · cited 4×
“Importantly, pancreata from compound mutant animals did not express detectable levels of p21, a cell cycle inhibitor and p53 target gene (Figure 3C), arguing against the possibility that the decreased proliferative rates of acinar and islet cells compared with PanINs were due to Ras-induced senescence in the former ce…”
BackgroundInfluentialMice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Butel, J. S., & Bradley, A. (1992) · Nature · doi:10.1038/356215a0 · Cited by 4,649
Jemal, A., Murray, T., Samuels, A., Ghafoor, A., Ward, E., & Thun, M. J. (2003) · CA: A Cancer Journal for Clinicians · doi:10.3322/canjclin.53.1.5 · Cited by 3,275
Use of proteomic patterns in serum to identify ovarian cancer
Petricoin, E. F., Ardekani, A. M., Hitt, B. A., Levine, P. J., Fusaro, V. A., Steinberg, S. M., Mills, G. B., Simone, C., Fishman, D. A., Kohn, E. C., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)07746-2 · Cited by 3,236
Self-citationTumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes
Land, H., Parada, L. F., & Weinberg, R. A. (1983) · Nature · doi:10.1038/304596a0 · Cited by 2,804
Matrix Metalloproteinase Inhibitors and Cancer—Trials and Tribulations
Coussens, L. M., Fingleton, B., & Matrisian, L. M. (2002) · Science · doi:10.1126/science.1067100 · Cited by 2,761
Tumor spectrum analysis in p53-mutant mice
Jacks, T., Remington, L., Williams, B. O., Schmitt, E. M., Halachmi, S., Bronson, R. T., & Weinberg, R. A. (1994) · Current Biology · doi:10.1016/s0960-9822(00)00002-6 · Cited by 2,051
Self-citationAnalysis of lung tumor initiation and progression using conditional expression of oncogenic K-rasPreprint
Jackson, E. L., Willis, N. A., Mercer, K. L., Bronson, R. T., Crowley, D. G., Montoya, R., Jacks, T., & Tuveson, D. A. (2001) · Genes & Development · doi:10.1101/gad.943001 · Cited by 1,927
Self-citationPancreatitis and the Risk of Pancreatic Cancer
Lowenfels, A. B., Maisonneuve, P., Cavallini, G., Ammann, R., Lankisch, P. G., Andersen, J. R., DiMagno, E. P., Andrén‐Sandberg, Å., & Domellöf, L. (1993) · New England Journal of Medicine · doi:10.1056/nejm199305203282001 · Cited by 1,753
Role of the INK4a Locus in Tumor Suppression and Cell Mortality
Serrano, M., Lee, H.-W., Chin, L., Cordon-Cardo, C., Beach, D., & DePinho, R. A. (1996) · Cell · doi:10.1016/s0092-8674(00)81079-x · Cited by 1,585
PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum
Offield, M. F., Jetton, T. L., Labosky, P. A., Ray, M., Stein, R. W., Magnuson, M. A., Hogan, B. L. M., & Wright, C. V. E. (1996) · Development · doi:10.1242/dev.122.3.983 · Cited by 1,514
Self-citationRuley, H. E. (1983) · Nature · doi:10.1038/304602a0 · Cited by 1,248
Warshaw, A. L., & Castillo, C. F. F.-D. (1992) · New England Journal of Medicine · doi:10.1056/nejm199202133260706 · Cited by 1,200
Somatic activation of the K-ras oncogene causes early onset lung cancer in mice
Johnson, L., Mercer, K., Greenbaum, D., Bronson, R. T., Crowley, D., Tuveson, D. A., & Jacks, T. (2001) · Nature · doi:10.1038/35074129 · Cited by 1,179
Self-citationNotch signalling controls pancreatic cell differentiation
Apelqvist, Å., Li, H., Sommer, L., Beatus, P., Anderson, D. J., Honjo, T., de Angelis, M. H., Lendahl, U., & Edlund, H. (1999) · Nature · doi:10.1038/23716 · Cited by 1,158
Control of endodermal endocrine development by Hes-1
Jensen, J. N., Pedersen, E. E., Galante, P. E., Hald, J., Heller, R. S., Ishibashi, M., Kageyama, R., Guillemot, F., Serup, P., & Madsen, O. D. (2000) · Nature Genetics · doi:10.1038/71657 · Cited by 1,155
Matrix metalloproteinases: a tail of a frog that became a prince
Brinckerhoff, C., & Matrisian, L. M. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm763 · Cited by 1,112
Aguirre, A. J., Bardeesy, N., Sinha, M., Lopez, L., Tuveson, D. A., Horner, J., Redston, M. S., & DePinho, R. A. (2003) · Genes & Development · doi:10.1101/gad.1158703 · Cited by 1,033 · cited 1×
“…the LSL-KRASG12D mice Revised: November 26, 2003described here, it has recently been shown that pancreatic exPublished: December 10, 2003pression of oncogenic KRAS in the context of INK4a/ARF deficiency results in PDA with very short latency and high pene- References trance (Aguirre et al., 2003).”
BackgroundSelf-citationThe role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors
Kawaguchi, Y., Cooper, B., Gannon, M., Ray, M., MacDonald, R. J., & Wright, C. V. E. (2002) · Nature Genetics · doi:10.1038/ng959 · Cited by 1,007 · cited 7×
“, 2001) and P48 mice (Kawaguchi et al., 2002) were previously described.”
BackgroundInfluentialSelf-citationLi, J., Zhang, Z., Rosenzweig, J. M., Wang, Y. Y., & Chan, D. W. (2002) · Clinical Chemistry · doi:10.1093/clinchem/48.8.1296 · Cited by 885
Progression model for pancreatic cancer.
Hruban, R. H., Goggins, M., Parsons, J., & Kern, S. E. (2000) · PubMed · Cited by 872
Self-citationγ-Secretase-mediated proteolysis in cell-surface-receptor signalling
Fortini, M. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm910 · Cited by 827
Yeo, C. J., Cameron, J. L., Lillemoe, K. D., et al. (2002) · Annals of Surgery · doi:10.1097/00000658-200209000-00012 · Cited by 811
Understanding Ras: ‘it ain’t over ’til it’s over’
Shields, J. M., Pruitt, K., McFall, A. J., Maddox, A. S., & Der, C. J. (2000) · Trends in Cell Biology · doi:10.1016/s0962-8924(00)01740-2 · Cited by 784
Sandgren, E. P., Luetteke, N., Palmiter, R. D., Brinster, R. L., & Lee, D. C. (1990) · Cell · doi:10.1016/0092-8674(90)90075-p · Cited by 752
Co-expression of multiple transgenes in mouse CNS: a comparison of strategies
Jankowsky, J. L., Slunt, H. H., Ratovitski, T., Jenkins, N. A., Copeland, N. G., & Borchelt, D. R. (2001) · Biomolecular Engineering · doi:10.1016/s1389-0344(01)00067-3 · Cited by 746
Serum Proteomic Patterns for Detection of Prostate Cancer
Petricoin, E. F. (2002) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/94.20.1576 · Cited by 728
Self-citationCyclooxygenase-2 expression is up-regulated in human pancreatic cancer.
Tucker, O., Dannenberg, A. J., Yang, E. K., Zhang, F., Teng, L., Daly, J. M., Soslow, R. A., Masferrer, J. L., Woerner, B. M., Koki, A. T., et al. (1999) · PubMed · Cited by 690
Notch mediates TGFα-induced changes in epithelial differentiation during pancreatic tumorigenesis
Miyamoto, Y., Maitra, A., Ghosh, B., Zechner, U., Argani, P., Iacobuzio-Donahue, C. A., Sriuranpong, V., Iso, T., Meszoely, I. M., Wolfe, M. S., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00140-5 · Cited by 643
Self-citationAdam, B.-L., Qu, Y., Davis, J. W., Ward, M. D., Clements, M. A., Cazares, L. H., Semmes, O. J., Schellhammer, P. F., Yasui, Y., Feng, Z., et al. (2002) · PubMed · Cited by 608
Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin
Wilson, C. L., Goss, K. H., Labosky, P. A., Hogan, B. L. M., & Matrisian, L. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.4.1402 · Cited by 603
Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context
Guerra, C. E., Mijimolle, N., Dhawahir, A., Dubus, P. R., Barradas, M., Serrano, M., Campuzano, V., & Barbacid, M. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00191-0 · Cited by 577
Clinical proteomics: Written in blood
Liotta, L. A., Ferrari, M., & Petricoin, E. F. (2003) · Nature · doi:10.1038/425905a · Cited by 546
Self-citationKrapp, A., Knöfler, M., Ledermann, B., Bürki, K., Berney, C., Zoerkler, N., Hagenbüchle, O., & Wellauer, P. K. (1998) · Genes & Development · doi:10.1101/gad.12.23.3752 · Cited by 529
Sirard, C., de la Pompa, J. L., Elia, A., Itié, A., Mirtsos, C., Cheung, A., Hahn, S. A., Wakeham, A. C., Schwartz, L., Kern, S. E., et al. (1998) · Genes & Development · doi:10.1101/gad.12.1.107 · Cited by 498
Genetic progression in the pancreatic ducts
Hruban, R. H., Wilentz, R. E., & Kern, S. E. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65054-7 · Cited by 373
Self-citationMorphological lesions associated with human primary invasive nonendocrine pancreas cancer.
Cubilla, A. L., & FITZGERALD, P. J. (1976) · PubMed · Cited by 352
Yeo, T. P., Hruban, R. H., Leach, S. D., Wilentz, R. E., Sohn, T. A., Kern, S. E., Iacobuzio–Donahue, C. A., Maitra, A., Goggins, M., Canto, M. I., et al. (2002) · Current Problems in Cancer · doi:10.1067/mcn.2002.129579 · Cited by 321
Self-citationBrca2 is required for embryonic cellular proliferation in the mouse.Preprint
Suzuki, A., de la Pompa, J. L., Hakem, R., Elia, A., Yoshida, R., Mo, R., Nishina, H., Chuang, T., Wakeham, A. C., Itié, A., et al. (1997) · Genes & Development · doi:10.1101/gad.11.10.1242 · Cited by 286
Signaling and transcriptional control of pancreatic organogenesis
Kim, S. K. (2002) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00338-6 · Cited by 239
Morphological patterns of primary nonendocrine human pancreas carcinoma.
Cubilla, A. L., & FITZGERALD, P. J. (1975) · PubMed · Cited by 231
Crawford, H. C., Scoggins, C. R., Washington, M. K., Matrisian, L. M., & Leach, S. D. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215051 · Cited by 226
Self-citationJaffee, E. M., Hruban, R. H., Canto, M. I., & Kern, S. E. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00093-4 · Cited by 222
Self-citationGrippo, P. J., Nowlin, P. S., Demeure, M. J., Longnecker, D. S., & Sandgren, E. P. (2003) · PubMed · Cited by 207
Wagner, M., Greten, F. R., Weber, C. K., Koschnick, S., Mattfeldt, T., Deppert, W., Kern, H. F., Adler, G., & Schmid, R. M. (2001) · Genes & Development · doi:10.1101/gad.184701 · Cited by 204
K-ras mutations in pancreatic ductal proliferative lesions.
Klimstra, D. S., & Longnecker, D. S. (1994) · PubMed · Cited by 197
WAGNER, M., Lührs, H., Klöppel, G., Adler, G., & Schmid, R. M. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70098-8 · Cited by 193
Brembeck, F. H., Schreiber, F. S., Deramaudt, T. B., Craig, L. E., Rhoades, B., Swain, G. P., Grippo, P. J., Stoffers, D. A., Silberg, D. G., & Rustgi, A. K. (2003) · PubMed · Cited by 190
The matrix metalloproteinase matrilysin influences early-stage mammary tumorigenesis.
Rudolph‐Owen, L. A., Chan, R., Muller, W. J., & Matrisian, L. M. (1998) · PubMed · Cited by 162
Association Between Nonsteroidal Anti-Inflammatory Drug Use and the Incidence of Pancreatic Cancer
Anderson, K. E. (2002) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/94.15.1168 · Cited by 160
Cyclooxygenase 2 Expression in Pancreatic Adenocarcinoma and Pancreatic Intraepithelial Neoplasia
Maitra, A., Ashfaq, R., Gunn, C. R., Rahman, A., Yeo, C. J., Sohn, T. A., Cameron, J. L., Hruban, R. H., & Wilentz, R. E. (2002) · American Journal of Clinical Pathology · doi:10.1309/tpg4-ck1c-9v8v-8awc · Cited by 159
Self-citationEarly detection of pancreatic carcinoma
Rosty, C., & Goggins, M. (2002) · Hematology/Oncology Clinics of North America · doi:10.1016/s0889-8588(01)00007-7 · Cited by 141
Allison, D. C., Piantadosi, S., Hruban, R. H., Dooley, W. C., Fishman, E. K., Yeo, C. J., Lillemoe, K. D., Pitt, H. A., Lin, P., & Cameron, J. L. (1998) · Journal of Surgical Oncology · doi:10.1002/(sici)1096-9098(199803)67:3 · Cited by 122
Self-citationA white paper: the product of a pancreas cancer think tank.
Kern, S. E., Hruban, R. H., Hollingsworth, M. A., Brand, R. E., Adrian, T. E., Jaffee, E. M., & Tempero, M. A. (2001) · PubMed · Cited by 114
Self-citationMatrix Metalloproteinase Inhibitors and Cancer
Summers, J. B., & Davidsen, S. K. (1998) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(08)61078-7 · Cited by 59
Recent advances in the development of gamma-secretase inhibitors.
Josien, H. B. (2002) · PubMed · Cited by 40
Urgell, E., Puig, P., Boadas, J., Capellá, G., Queraltó, J. M., Boluda, R., Antonijuan-Parés, A., Farré, A., Lluı́s, F., González‐Sastre, F., et al. (2000) · European Journal of Cancer · doi:10.1016/s0959-8049(00)00288-4 · Cited by 18
In Search of an Early Warning System for Pancreatic Cancer
Hingorani, S. R., & Tuveson, D. A. (2003) · Cancer Biology & Therapy · doi:10.4161/cbt.246 · Cited by 14
Self-citation
Research works printed but not linked: 1
- Kern, 2001, A white paper, Cancer Res., 61, 4923
Cited by
Sorted by citations
Glypican-1 identifies cancer exosomes and detects early pancreatic cancer
Melo, S. A., Luecke, L. B., Kahlert, C., Fernandez, A. F., Gammon, S. T., Kaye, J., LeBleu, V. S., Mittendorf, E. A., Weitz, J., Rahbari, N., et al. (2015) · Nature · doi:10.1038/nature14581 · Cited by 2,880
Özdemir, B. C., Pentcheva-Hoang, T., Carstens, J. L., Zheng, X., Wu, C.-C., Simpson, T. R., Laklai, H., Sugimoto, H., Kahlert, C., Novitskiy, S. V., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.005 · Cited by 2,681
Self-citationHingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609
Self-citationA complex secretory program orchestrated by the inflammasome controls paracrine senescence
Acosta, J. C., Banito, A., Wuestefeld, T., Georgilis, A., Janich, P., Morton, J. P., Athineos, D., Kang, T.-W., Lasitschka, F., Andrulis, M., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2784 · Cited by 2,278
Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
DeNicola, G. M., Karreth, F. A., Humpton, T. J., Gopinathan, A., Wei, C., Frese, K., Mangal, D., Yu, K. H., Yeo, C. J., Calhoun, E. S., et al. (2011) · Nature · doi:10.1038/nature10189 · Cited by 2,277
Self-citation
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.
- ORCID
- 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
- bronze
- doi.org
- Licence
- 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
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
