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The lsktm1 locus modulates lung and skin tumorigenesis in the mouse

TitleThe lsktm1 locus modulates lung and skin tumorigenesis in the mouse
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2012
AuthorsGalvan, A., Colombo F., Noci S., Pazzaglia Simonetta, Mancuso Mariateresa, Manenti G., Broman K.W., Saran Anna, and Dragani T.A.
JournalG3: Genes, Genomes, Genetics

Alleles derived from skin tumor2resistant 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. © 2012 Galvan et al.


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Citation KeyGalvan20121041