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Precancer in Mice: Animal Models Used to Understand, Prevent, and Treat Human Precancers

¹ The UCD Center for Comparative Medicine, University of California, Davis, Davis, California 95616, USA
² Pathology/Histotechnology Laboratory, SAIC Frederick, Inc./NCI-Frederick, Frederick, Maryland 21702, USA
³ Veterans Affairs Medical Center and University of Cincinnati, Department of Pathology and Laboratory Medicine, Cincinnati, Ohio 45220, USA
⁴ Department of Pathology, University of Vermont, Burlington, Vermont 05405, USA
⁵ Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA
⁶ Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892, USA
⁷ Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, New York 14853, USA
⁸ Pathology Department, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, USA
⁹ Department of Pathology, UCLA, Los Angeles, California 90095, USA
¹⁰ Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, Distric of Columbia 20057, USA
¹¹ Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, NIH, and SoBran, Inc., Bethesda, Maryland 20892-8135, USA

Correspondence: Address correspondence to: Robert D. Cardiff, Center for Comparative Medicine, Hutchison Drive and CR 98, University of Califonia, Davis, Davis, CA 95616, USA. e-mail:rdcardif{at}ucdavis.edu

We present a status report from the NCI Mouse Models of Human Cancers Consortium (MMHCC) Precancers Workshop held November 8 and 9, 2004. An expert panel, the Mouse Models Group (MMG) evaluated the status of mouse models of precancer emphasizing genetically engineered mouse models, especially of lining epithelium and their utilitarian value to human carcinogenesis. An outline of the background for the panel’s considerations is provided with examples of past and current precancerous lesions in mice. The experimental use of oncogenic viruses and chemical carcinogens in mice led to operational definitions of initiation, promotion, and preneoplasia Preneoplastic and precancerous lesions are found in these models. In this precancer concept, most preneoplastic lesions are considered as potentially precancerous or at least an earlier stage in cancer development than typical pre-invasive epithelial lesions, which are often seen in these mouse models. Genetically engineered mice, used to test the oncogenicity of individual genes, develop precancers that are initiated by defined molecular and histopathologic changes. The mouse can be used to isolate and study precancers in detail, thereby providing a level of biological understanding not readily available in clinical disease. These studies suggest that genetically engineered mice are very useful preclinical models for chemoprevention and therapy.

Key Words: Precancer • mouse • models • GEM (Genetic Engineered Mice) • pathology • preclinical • trials

Abbreviations: ACF, aberrant crypt foci • BCAC, B-catenin-accumulated crypts • DMBA, 7, 12-dimethylbenz(a)anthracene • GEM, genetically engineered mouse • HAN, hyperplastic alveolar nodule • mGIN, mouse gastrointestinal neoplasia • MMG, Mouse Models Group • MMHCC, Mouse Models of Human Cancers Consortium • mMIN, mouse mammary intraepithelial neoplasia • MMTV, mouse mammary tumor virus • mPIN, murine prostatic intraepithelial neoplasia • mSkIN, mouse skin intraepithelial neoplasia • SENCAR, sensitivity to carcinogens • TPA, 12-O-tetradecanoyl-phorbol-13-acetate

Toxicologic Pathology, Vol. 34, No. 6, 699-707 (2006)
DOI: 10.1080/01926230600930129


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