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Polygenic resistance to mouse pulmonary adenomas
H Hiai1, P Abujiang, M Nishimura
1Department of Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine, Kyoto, Japan. hiai@path1.med.kyoto-u.ac.jp
Experimental Lung Research
|February 24, 2001
Summary
Researchers identified two dominant resistance genes, Par1 and Par3, in mice that protect against lung tumors. These findings suggest potential therapeutic targets for human lung cancer, particularly adenocarcinoma.
Area of Science:
- Genetics
- Cancer Research
- Mouse Models
Background:
- Susceptibility to urethane-induced pulmonary adenomas (PA) in mice is genetically complex.
- Recombinant inbred (RI) mouse strains are valuable tools for dissecting complex genetic traits.
Purpose of the Study:
- To identify genetic loci controlling resistance to pulmonary adenomas in mice.
- To investigate the relevance of these resistance loci to human lung cancer.
Main Methods:
- Generation and analysis of SMXA RI mouse strains from a cross between susceptible A/J and resistant SM/J mice.
- Quantitative trait locus (QTL) analysis and genome scanning to identify resistance loci.
- Analysis of loss of heterozygosity (LOH) in human lung cancer samples.
Main Results:
- Two novel dominant resistance loci, Par1 on MMU11 and Par3 on MMU12, were identified in mice.
- These loci were epistatic to the major susceptibility locus Pas1.
- Loss of heterozygosity at syntenic human chromosomal regions 17q and 14q was observed in lung cancer patients, with differential patterns for adenocarcinoma versus squamous cell and small cell carcinomas.
Conclusions:
- Dominant resistance genes in mice can influence susceptibility to chemically induced lung tumors.
- The identified mouse resistance loci have syntenic regions in humans associated with lung cancer, suggesting conserved mechanisms.
- Further investigation of Par1 and Par3 homologs may offer insights into human lung cancer development and potential therapeutic strategies.