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G3 (Bethesda). 2012 Sep;2(9):1041-6. doi: 10.1534/g3.112.003525. Epub 2012 Sep 1.

The Lsktm1 locus modulates lung and skin tumorigenesis in the mouse.

Author information

1
Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.

Abstract

Alleles derived from skin tumor-resistant Car-R mice provide resistance to both skin and lung tumorigenesis over the susceptibility of the SWR/J strain. In an effort to map tumor modifier loci affecting both tumor types, we carried out a genetic linkage analysis in backcross SWR/J x (SWR/J x Car-R) mice and identified a locus (Lsktm1) on chromosome 1 linked to both skin (LOD score = 3.93) and lung (LOD score = 8.74) tumorigenesis. Two genes, Igfbp5 and Igfbp2, residing in this locus and belonging to the insulin-like growth factor binding protein family were expressed at significantly greater levels in normal lung tissue from cancer-resistant Car-R mice than in cancer-susceptible SWR/J mice. Overexpression of the recombinant Igfbp5 and Igfbp2 genes in two lung cancer cell lines significantly inhibited clonogenicity (P < 0.0001). Collectively, we have identified a single polymorphic locus that affects skin and lung tumorigenesis and identify Igfbp5 and Igfbp2 as candidate modifier genes of lung tumorigenesis.

KEYWORDS:

cancer modifier genes; disease models; lung cancer; quantitative trait loci (QTLs); single-nucleotide polymorphisms; skin cancer

PMID:
22973541
PMCID:
PMC3429918
DOI:
10.1534/g3.112.003525
[Indexed for MEDLINE]
Free PMC Article
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