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Updated: Feb 5, 2026
Orthotopic Mouse Model of Colorectal Cancer
Published on: December 4, 2007
MOLECULAR FEATURES AND MOUSE MODELS OF COLORECTAL CANCER
1ANN ARBOR, MICHIGAN.
Abstract:
Colorectal cancers (CRCs) harbor accumulated defects in key signaling pathways that regulate cell phenotypes, including proliferation, survival, metabolism, and differentiation. To study the functional contributions of the accumulated molecular defects in CRC, we have developed approaches to inactivate selected tumor suppressor and/or activate oncogenes in mouse colon epithelium. Conditional inactivation of the CDX2 tumor suppressor protein in conjunction with oncogenic activation of the BRAF protein promotes development of serrated glandular benign and malignant tumors in the mouse colon. The mouse tumors share significant morphological and molecular relationships with the 8% to 10% of human CRCs that manifest serrated morphology at diagnosis. The gene and protein expression patterns in the mouse tumors have informed understanding of the relationships between benign and malignant human serrated colon tumors. Our findings are consistent with prior work suggesting that perhaps upwards of one-third of human CRCs may arise from a precursor lesion with serrated morphology rather than a conventional adenoma.
Insights
Researchers modeled colorectal cancer (CRC) in mice by altering CDX2 and BRAF genes. This study reveals insights into serrated colorectal tumors, which represent a significant subset of human CRCs.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Colorectal cancers (CRCs) arise from accumulated defects in signaling pathways governing cell behavior.
- Understanding these molecular defects is crucial for developing effective CRC treatments.
Purpose of the Study:
- To investigate the functional impact of specific molecular defects in mouse colon epithelium.
- To model serrated colorectal tumors by manipulating key genes.
Main Methods:
- Developed methods to conditionally inactivate tumor suppressor genes (CDX2) and activate oncogenes (BRAF) in mouse colon epithelium.
- Analyzed the resulting tumors for morphological and molecular similarities to human CRCs.
Main Results:
- Inactivation of CDX2 combined with BRAF activation promoted benign and malignant serrated glandular tumors in mice.
- These mouse tumors exhibited significant morphological and molecular parallels with human serrated CRCs.
- Gene and protein expression patterns provided insights into the progression of serrated colon tumors.
Conclusions:
- The mouse model effectively recapitulates key features of human serrated colorectal cancers.
- Findings support the hypothesis that a substantial proportion of CRCs may originate from serrated precursor lesions.
- This research enhances understanding of the molecular underpinnings of serrated CRC subtypes.
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