Pulmonary adenoma susceptibility 1 (Pas1) locus affects inflammatory response

Durvanei Augusto Maria, Giacomo Manenti, Federica Galbiati, Orlando Garcia Ribeiro, Wafa Hanna Koury Cabrera, Roberto Giannì Barrera, Angela Pettinicchio, Marcelo De Franco, Nancy Starobinas, Maria Siqueira, Tommaso A. Dragani, Olga Martinez Ibañez

Research output: Contribution to journalArticlepeer-review

Abstract

Two outbred mouse lines, phenotypically selected for differential subcutaneous (s.c.) acute inflammatory response (AIR), were analysed for urethane-induced lung inflammatory response and susceptibility to lung tumorigenesis. AIR min mice, which show a low response to s.c. acute inflammation, developed a persistent subacute lung inflammatory response and a 40-fold higher lung tumor multiplicity than did AIR max mice, which are selected for high response to s.c. acute inflammation and showed a transient lung inflammatory response. A highly significant linkage disequilibrium pattern was observed in AIR max and AIR min mice at marker alleles located within a 452-kb pulmonary adenoma susceptibility 1 (Pas1) locus region, thus defining the location of gene candidacy for inflammatory response and for the biological effects of Pas1 in this region. AIR min and AIR max mice segregated by descent the Pas1 s and Pas1 r alleles, respectively, providing evidence for the involvement of the Pas1 locus in the inflammatory response. The 452-kb region contains Kras2 and four additional genes, including the lymphoid-restricted membrane protein (Lrmp) gene, whose Pro→ Leu nonconservative variation was linked with inflammatory response and Pas1 allelotype. These results provide a model to explore the mechanism underlying inherited predisposition to lung cancer in the context of a link to inflammation.

Original languageEnglish
Pages (from-to)426-432
Number of pages7
JournalOncogene
Volume22
Issue number3
DOIs
Publication statusPublished - Jan 23 2003

Keywords

  • Cancer modifier loci
  • Genetic polymorphisms
  • Linkage disequilibrium
  • Pas1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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