ArticleProceedings of the National Academy of Sciences of the United States of America2006
Loss of Apc allows phenotypic manifestation of the transforming properties of an endogenous K-ras oncogene in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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118 citing papers in PubMed, 189 citations in OpenAlex.
- Dynamic transitioning between MAPK-driven and WNT-driven cell states drives intestinal cancer and shapes therapy response.Nature genetics · 2026Article
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- Inactivation of necroptosis-promoting protein MLKL creates a therapeutic vulnerability in colorectal cancer cells.Cell death & disease · 2025Article
- Development of a new flippase-dependent mouse model for red fluorescence-based isolation of KRASTransgenic research · 2025Article
- Recent advances in the development and application of colorectal cancer mouse models.Frontiers in pharmacology · 2025Review
- Evolutionary dependency of cancer mutations in gene pairs inferred by nonsynonymous-synonymous mutation ratios.Genome medicine · 2024Article
- Development of a new flippase-dependent mouse model for red fluorescence-based isolation of KrasbioRxiv : the preprint server for biology · 2024Article
- Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers.Cancer discovery · 2024Article
- Colorectal cancer murine models: Initiation to metastasis.Cancer letters · 2024Review
- Enhanced bacterial cancer therapy delivering therapeutic RNA interference of c-Myc.Cell & bioscience · 2024Article
- KRAS allelic imbalance drives tumour initiation yet suppresses metastasis in colorectal cancer in vivo.Nature communications · 2024Article
- Article
- Mouse models in colon cancer, inferences, and implications.iScience · 2023Review
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- Analysis of the Whole-Genome Sequences from anGenes · 2022Article
- Recruiting Immunity for the Fight against Colorectal Cancer: Current Status and Challenges.International journal of molecular sciences · 2022Review
- Mouse models of Kras activation in gastric cancer.Experimental & molecular medicine · 2022Review
- Mouse Models for Application in Colorectal Cancer: Understanding the Pathogenesis and Relevance to the Human Condition.Biomedicines · 2022Review
- Article
58 more citing papers are in PubMed but not listed here.
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11 authors at 3 institutions in 2 countries.
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Abstract
Oncogenic mutations in the K-ras gene occur in approximately 50% of human colorectal cancers. However, the precise role that K-ras oncogenes play in tumor formation is still unclear. To address this issue, we have conditionally expressed an oncogenic K-ras(V12) allele in the small intestine of adult mice either alone or in the context of Apc deficiency. We found that expression of K-ras(V12) does not affect normal intestinal homeostasis or the immediate phenotypes associated with Apc deficiency. Mechanistically we failed to find activation of the Raf/MEK/ERK pathway, which may be a consequence of the up-regulation of a number of negative feedback loops. However, K-ras(V12) expression accelerates intestinal tumorigenesis and confers invasive properties after Apc loss over the long term. In renal epithelium, expression of the oncogenic K-ras(V12) allele in the absence of Apc induces the rapid development of renal carcinoma. These tumors, unlike those of intestinal origin, display activation of the Raf/MEK/ERK and Akt signaling pathways. Taken together, these data indicate that normal intestinal and kidney epithelium are resistant to malignant transformation by an endogenous K-ras oncogene. However, activation of K-ras(V12) after Apc loss results in increased tumorigenesis with distinct kinetics. Whereas the effect of K-ras oncogenes in the intestine can been observed only after long latencies, they result in rapid carcinogenesis in the kidney epithelium. These data imply a window of opportunity for anti-K-ras therapies after tumor initiation in preventing tumor growth and invasion.
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