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Lung cancer-associated SNP at the beginning of mouse k-ras gene intron 2 is essential for transcription factor

E V Gorshkova1, V I Kaledin, V F Kobzev

  • 1Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences, Novosibirsk. schly@mail.ru

Bulletin of Experimental Biology and Medicine
|March 17, 2007
PubMed

Insights

A specific gene mutation in lung cancer-resistant mice (M. spretus) weakens a transcription factor binding site compared to sensitive mice (M. musculus), affecting gene regulation.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • The K-ras gene plays a crucial role in cell growth and is frequently mutated in various cancers, including lung cancer.
  • Differences in K-ras gene regulation and associated transcription factor binding can influence susceptibility to diseases like lung cancer.
  • Comparative studies between different mouse strains with varying disease resistance offer insights into genetic determinants of cancer.

Purpose of the Study:

  • To investigate the molecular basis of differential lung cancer resistance between M. spretus and M. musculus mice.
  • To identify genetic variations in the K-ras gene and their impact on transcription factor binding.
  • To elucidate the role of K-ras gene regulation in lung cancer susceptibility.

Main Methods:

  • DNA sequencing of the K-ras gene intron 2 in M. spretus and M. musculus mice.
  • Analysis of transcription factor binding sites, specifically for NF-Y, within the K-ras gene.
  • Electrophoretic mobility shift assays (EMSA) or similar techniques to assess nuclear protein binding to K-ras DNA fragments.

Main Results:

  • A specific C to T substitution at position 311 in the K-ras gene intron 2 was identified in lung cancer-resistant M. spretus mice.
  • This substitution was found to attenuate the binding site for the NF-Y transcription factor in M. spretus compared to M. musculus.
  • Significant differences in the general pattern of nuclear protein binding to a 248-332 nucleotide pair fragment of the K-ras gene were observed between the two mouse strains.

Conclusions:

  • The identified C to T substitution in the K-ras gene intron 2 is a key genetic difference contributing to lung cancer resistance in M. spretus.
  • Attenuation of NF-Y transcription factor binding due to this mutation likely alters K-ras gene expression and downstream signaling pathways.
  • These findings highlight the importance of specific genetic variations in K-ras in determining cancer susceptibility and provide a molecular basis for observed resistance.

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