The lsktm1 locus modulates lung and skin tumorigenesis in the mouse

Antonella Galvan, Francesca Colombo, Sara Noci, Simonetta Pazzaglia, Mariateresa Mancuso, Giacomo Manenti, Karl W. Broman, Anna Saran, Tommaso A. Dragani

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1041-1046
Number of pages6
JournalG3: Genes, Genomes, Genetics
Volume2
Issue number9
DOIs
Publication statusPublished - Sep 2012

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Keywords

  • Cancer modifier
  • Disease models
  • Genes
  • Loci (QTLs)
  • Lung cancer
  • Polymorphisms
  • Quantitative trait
  • Single-nucleotide
  • Skin cancer

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Genetics(clinical)

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