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Updated: Apr 21, 2026

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer
Published on: July 6, 2017
Decreased tumorigenesis in mice with a Kras point mutation at C118
Lu Huang1, John Carney2, Diana M Cardona2
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Abstract:
KRAS, NRAS or HRAS genes are mutated to encode an active oncogenic protein in a quarter of human cancers. Redox-dependent reactions can also lead to Ras activation in a manner dependent upon the thiol residue of cysteine 118 (C118). Here, to investigate the effect of mutating this residue on tumorigenesis, we introduce a C118S mutation into the endogenous murine Kras allele and expose the resultant mice to the carcinogen urethane, which induces Kras mutation-positive lung tumours. We report that Kras(+/C118S) and Kras(C118S/C118S) mice develop fewer lung tumours. Although the Kras(C118S) allele does not appear to affect tumorigenesis when the remaining Kras allele is conditionally oncogenic, there is a moderate imbalance of oncogenic mutations favouring the native Kras allele in tumours from Kras(+/C118S) mice treated with urethane. We conclude that the Kras(C118S) allele impedes urethane-induced lung tumorigenesis.
Insights
The Kras(C118S) mutation reduces lung tumor development in mice exposed to urethane. This suggests the cysteine 118 residue in Kras is important for tumorigenesis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ras proteins (KRAS, NRAS, HRAS) are frequently oncogenic in human cancers.
- Ras activation can be redox-dependent, involving cysteine 118 (C118).
Purpose of the Study:
- To investigate the role of Kras C118 in tumorigenesis.
- To determine the effect of a C118S mutation on lung tumor development.
Main Methods:
- Introduction of a C118S mutation into the endogenous murine Kras allele.
- Exposure of resultant mice to the carcinogen urethane.
- Analysis of lung tumor incidence and oncogenic mutation patterns.
Main Results:
- Mice with Kras(C118S) alleles developed fewer urethane-induced lung tumors.
- The Kras(C118S) allele impeded tumorigenesis, particularly in urethane-treated mice.
- An imbalance favoring the native Kras allele was observed in tumors from heterozygous mice.
Conclusions:
- The Kras(C118S) mutation impedes urethane-induced lung tumorigenesis.
- The C118 residue in Kras plays a role in cancer development.
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