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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
G3 (Bethesda, Md.) | 2012

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.

Pubmed ID: 22973541

Research resources used in this publication

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM074244
  • Agency: NIGMS NIH HHS, United States
    Id: GM074244

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Ensembl (tool)

RRID:SCR_002344

Collection of genome databases for vertebrates and other eukaryotic species with DNA and protein sequence search capabilities. Used to automatically annotate genome, integrate this annotation with other available biological data and make data publicly available via web. Ensembl tools include BLAST, BLAT, BioMart and the Variant Effect Predictor (VEP) for all supported species.

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BRB-ArrayTools (tool)

RRID:SCR_010938

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UniGene (tool)

RRID:SCR_004405

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on January 11, 2023. Web tool for an organized view of the transcriptome. Collection of the computationally identified transcripts from the same locus. Information on protein similarities, gene expression, cDNA clones, and genomic location. System for automatically partitioning GenBank sequences into a non redundant set of gene oriented clusters.

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R/QTL (tool)

RRID:SCR_009085

Software program for mapping quantitative trait loci in experimental crosses. (entry from Genetic Analysis Software)

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NCI-H520 (tool)

RRID:CVCL_1566

Cell line NCI-H520 is a Cancer cell line with a species of origin Homo sapiens (Human)

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SWR/J (tool)

RRID:IMSR_JAX:000689

Mus musculus with name SWR/J from IMSR.

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