Cis-acting genetic elements at or near the Pas1 locus control Kras2 mutations and gene expression in lung tumors from mice selected for acute inflammatory response.

Abstract

Event Abstract Back to Event Cis-acting genetic elements at or near the Pas1 locus control Kras2 mutations and gene expression in lung tumors from mice selected for acute inflammatory response. Andrea Borrego1*, Antonella Galvan2, José R. Jensen1, Wafa Cabrera1, Orlando G. Ribeiro1, Nancy Starobinas1, Marcelo De Franco1, Olga M. Ibañez1, Giacomo Manenti2 and Tommaso A. Dragani2 1 Instituto Butantan, Laboratory of Immunogenetics, Brazil 2 Fondazione IRCCS Istituto Nazionale dei Tumori, Italy AIRmax (high response) and AIRmin (low response) mice, genetically selected for the intensity of acute inflammatory response (AIR), show divergent susceptibility for chemically-induced tumors, suggesting that genes which control acute inflammatory reactivity may modulate predisposition to tumorigenesis. AIRmax and AIRmin carry the resistance and susceptibility haplotypes, respectively, at Pas1 (Pulmonary adenoma susceptibility 1), the major locus regulating susceptibility to lung tumorigenesis in mice. The oncogene Kras2 maps at Pas1, and mutations of this gene are associated to lung tumor development. Our objective was to identify, through linkage analysis, chromosomal regions which control the mutability of Kras2 and the expression levels of Kras4A and Kras4B isoforms in lung tumors of intercrossed F2 (AIRmax x AIRmin) mice. Mice were treated at 7 days of age with 300 mg/kg urethane and after 9 months lung tumors were excised for DNA (n=500) and RNA (n=110) extraction. Kras2 activating mutations at codons 12, 13 and 61 were identified by DNA pyrosequencing. Expression levels of Kras isoforms and Lyrm5 (also mapping inside Pas1) were determined by qPCR. A panel of 1449 SNPs (single nucleotide polymorphisms) distributed in the whole genome, was tested for association with the mutability and expression phenotypes. One region at chromosome 6 (near to Pas1) was associated with Kras mutations (LOD 4.67). The expression levels of Kras4A, Kras4B isoforms and Lyrm5 showed association with Pas1 in chromosome 6 (LOD 3.16, 2.36 and 8.43 respectively). Results suggest the participation of cis-acting elements at or near Pas1 in the regulation of Kras2 mutability and expression. Acknowledgements Finantial support: The State of São Paulo Research Foundation (FAPESP) and National Council of Research (CNPq), Brazil and Associazione Italiana and Fondazione Italiana Ricerca Cancro (AIFIRC), Italy. Keywords: Inflammation, lung cancer, QTL, Urethane, Mice selected Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Borrego A, Galvan A, Jensen JR, Cabrera W, Ribeiro OG, Starobinas N, De Franco M, Ibañez OM, Manenti G and Dragani TA (2013). Cis-acting genetic elements at or near the Pas1 locus control Kras2 mutations and gene expression in lung tumors from mice selected for acute inflammatory response.. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00152 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Andrea Borrego, Instituto Butantan, Laboratory of Immunogenetics, Sao Paulo, Brazil, andreaborrego@butantan.gov.br Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Andrea Borrego Antonella Galvan José R Jensen Wafa Cabrera Orlando G Ribeiro Nancy Starobinas Marcelo De Franco Olga M Ibañez Giacomo Manenti Tommaso A Dragani Google Andrea Borrego Antonella Galvan José R Jensen Wafa Cabrera Orlando G Ribeiro Nancy Starobinas Marcelo De Franco Olga M Ibañez Giacomo Manenti Tommaso A Dragani Google Scholar Andrea Borrego Antonella Galvan José R Jensen Wafa Cabrera Orlando G Ribeiro Nancy Starobinas Marcelo De Franco Olga M Ibañez Giacomo Manenti Tommaso A Dragani PubMed Andrea Borrego Antonella Galvan José R Jensen Wafa Cabrera Orlando G Ribeiro Nancy Starobinas Marcelo De Franco Olga M Ibañez Giacomo Manenti Tommaso A Dragani Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.