| A functional switch from lung cancer resistance to susceptibility at the Pas1 locus in Kras2LA2 mice. | |
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MedLine Citation:
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PMID: 16823377 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pulmonary adenoma susceptibility 1 (Pas1) is the major mouse lung cancer susceptibility locus on chromosome 6 (ref. 1). Kras2 is a common target of somatic mutation in chemically induced mouse lung tumors and is a candidate Pas1 gene. M. spretus mice (SPRET/Ei) carry a Pas1 resistance haplotype for chemically induced lung tumors. We demonstrate that the SPRET/Ei Pas1 allele is switched from resistance to susceptibility by fixation of the parental origin of the mutant Kras2 allele. This switch correlates with low expression of endogenous Kras2 in SPRET/Ei. We propose that the Pas1 modifier effect is due to Kras2, and that a sensitive balance between the expression levels of wild-type and mutant alleles determines lung tumor susceptibility. These data demonstrate that cancer predisposition should also be considered in the context of somatic events and could have major implications for the design of human association studies to identify cancer susceptibility genes. |
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Authors:
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Minh D To; Jesus Perez-Losada; Jian-Hua Mao; Jeff Hsu; Tyler Jacks; Allan Balmain |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-07-02 |
Journal Detail:
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Title: Nature genetics Volume: 38 ISSN: 1061-4036 ISO Abbreviation: Nat. Genet. Publication Date: 2006 Aug |
Date Detail:
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Created Date: 2006-07-28 Completed Date: 2006-09-11 Revised Date: 2010-12-03 |
Medline Journal Info:
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Nlm Unique ID: 9216904 Medline TA: Nat Genet Country: United States |
Other Details:
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Languages: eng Pagination: 926-30 Citation Subset: IM |
Affiliation:
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University of California San Francisco (UCSF) Comprehensive Cancer Center, San Francisco, California 94115, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoma
/
chemically induced,
genetics Alleles Animals Carcinogens / toxicity Female Genetic Predisposition to Disease Lung Neoplasms / chemically induced, genetics* Male Mice Models, Genetic Mutation Oncogenes Proto-Oncogene Proteins p21(ras) / genetics* Risk Factors Urethane / toxicity |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA111834-01A2/CA/NCI NIH HHS; R01 CA111834-02/CA/NCI NIH HHS; R01 CA111834-03/CA/NCI NIH HHS; R01 CA111834-04/CA/NCI NIH HHS; U01CA84244/CA/NCI NIH HHS; U01CA84306/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Carcinogens; 51-79-6/Urethane; EC 3.6.5.2/Kras2 protein, mouse; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras) |
| Comments/Corrections | |
Comment In:
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Nat Genet. 2006 Aug;38(8):864-5
[PMID:
16874325
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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