Decreased tumorigenesis in mice with a Kras point mutation at C118.
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.
Duke Scholars
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Related Subject Headings
- Urethane
- Proto-Oncogene Proteins p21(ras)
- Point Mutation
- Mutagenesis, Site-Directed
- Mice, Transgenic
- Mice, Inbred C57BL
- Mice
- Male
- Lung Neoplasms
- Female
Citation
Published In
DOI
EISSN
Publication Date
Volume
Start / End Page
Location
Related Subject Headings
- Urethane
- Proto-Oncogene Proteins p21(ras)
- Point Mutation
- Mutagenesis, Site-Directed
- Mice, Transgenic
- Mice, Inbred C57BL
- Mice
- Male
- Lung Neoplasms
- Female