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Pulmonary adenoma susceptibility 1 (Pas1) locus affects inflammatory response

Oncogene volume 22, pages 426–432 (2003)Cite this article

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. AIRmin 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 AIRmax 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 AIRmax and AIRmin 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. AIRmin and AIRmax mice segregated by descent the Pas1s and Pas1r 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.

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Acknowledgements

This work was partially funded by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Associazione and Fondazione Italiana Ricerca Cancro (AIRC and FIRC) of Italy, and from the European Commission (Association Contract FIGHT-CT99-00006). M De Franco, N Starobinas, M Siqueira, and OM Ibañez were supported in part by Conselho Nacional de Pesquisas (CNPq). Roberto Gianní Barrera is a recipient of a FIRC fellowship.

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Author notes

  1. Durvanei Augusto Maria and Giacomo Manenti: These authors contributed equally to the work

Authors and Affiliations

  1. Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil

    Durvanei Augusto Maria, Orlando Garcia Ribeiro, Wafa Hanna Koury Cabrera, Marcelo De Franco, Nancy Starobinas, Maria Siqueira & Olga Martinez Ibañez

  2. Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy

    Giacomo Manenti, Federica Galbiati, Roberto Giannì Barrera, Angela Pettinicchio & Tommaso A Dragani

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  1. Durvanei Augusto Maria
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  2. Giacomo Manenti
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  3. Federica Galbiati
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  4. Orlando Garcia Ribeiro
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  6. Roberto Giannì Barrera
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  7. Angela Pettinicchio
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  8. Marcelo De Franco
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  9. Nancy Starobinas
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  10. Maria Siqueira
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  11. Tommaso A Dragani
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Corresponding author

Correspondence to Tommaso A Dragani.

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The data were deposited under GenBank Accession #: AJ437328 to AJ437336

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Maria, D., Manenti, G., Galbiati, F. et al. Pulmonary adenoma susceptibility 1 (Pas1) locus affects inflammatory response. Oncogene 22, 426–432 (2003). https://doi.org/10.1038/sj.onc.1206157

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