The Lsktm1 Locus Modulates Lung and Skin Tumorigenesis in the Mouse

G3: Genes, Genomes, Genetics

Francesca Colombo¹  Anna Saran²  Antonella Galvan¹  Karl W. Broman³  Simonetta Pazzaglia²  Giacomo Manenti¹  Sara Noci¹  Mariateresa Mancuso²  Tommaso A. Dragani¹ 

[1] Department of Predictive and Preventive Medicine; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyDepartment of Predictive and Preventive Medicine; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyDepartment of Predictive and Preventive Medicine; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l’Energia e lo Sviluppo Economico Sostenibile (ENEA) CR-Casaccia, Rome, ItalyLaboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l’Energia e lo Sviluppo Economico Sostenibile (ENEA) CR-Casaccia, Rome, ItalyLaboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l’Energia e lo Sviluppo Economico Sostenibile (ENEA) CR-Casaccia, Rome, Italy;Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Wisconsin 53706Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Wisconsin 53706Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Wisconsin 53706

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

DOI  :  10.1534/g3.112.003525

学科分类：生物科学（综合）

来源: Genetics Society of America

【 摘 要 】

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.

【 授权许可】

Unknown