First Author | Galvan A | Year | 2012 |
Journal | G3 (Bethesda) | Volume | 2 |
Issue | 9 | Pages | 1041-6 |
PubMed ID | 22973541 | Mgi Jnum | J:218370 |
Mgi Id | MGI:5617347 | Doi | 10.1534/g3.112.003525 |
Citation | Galvan A, et al. (2012) The Lsktm1 locus modulates lung and skin tumorigenesis in the mouse. G3 (Bethesda) 2(9):1041-6 |
abstractText | 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. |