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.

Nature Communications
|November 15, 2014
PubMed

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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