Expression quantitative trait analysis reveals fine germline transcript regulation in mouse lung tumors.
Gene expression modulates cellular functions in both physiologic and pathologic conditions. Herein, we carried out a genetic linkage study on the transcriptome of lung tumors induced by urethane in an (A/J x C57BL/6)F4 intercross population, whose individual lung tumor multiplicity (Nlung) is linked...
| Publicado en: | Cancer Letters Vol. 375; no. 2; pp. 221 - 231 |
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| Autores principales: | , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Elsevier B.V.
Jun2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=114483096&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 114483096 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03043835 3J8 jtl: Cancer Letters issn: 03043835 maglogo: N pubinfo: dt: Jun2016 vid: 375 iid: 2 pid: 1004 pub: Elsevier B.V. artinfo: ui: 114483096 114483096 NLM26966001 114483096 10.1016/j.canlet.2016.02.054 NLM26966001 114483096 ppf: 221 ppct: 10 formats: tig: atl: Expression quantitative trait analysis reveals fine germline transcript regulation in mouse lung tumors. aug: au: Cotroneo, Chiara E. Dassano, Alice Colombo, Francesca Pettinicchio, Angela Lecis, Daniele Dugo, Matteo De Cecco, Loris Dragani, Tommaso A. Manenti, Giacomo affil: Department of Predictive and Preventive Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy sug: subj: Lung Neoplasms Proteins Genetics Alleles Mice Genes Genotype Germ Cells Lung Neoplasms Pathology Disease Susceptibility Animal Studies Phosphotransferases Gene Expression Profiling Polymorphism, Genetic Phenotype ab: Gene expression modulates cellular functions in both physiologic and pathologic conditions. Herein, we carried out a genetic linkage study on the transcriptome of lung tumors induced by urethane in an (A/J x C57BL/6)F4 intercross population, whose individual lung tumor multiplicity (Nlung) is linked to the genotype at the Pulmonary adenoma susceptibility 1 (Pas1) locus. We found that expression levels of 1179 and 1579 genes are modulated by an expression quantitative trait locus (eQTL) in cis and in trans, respectively (LOD score > 5). Of note, the genomic area surrounding and including the Pas1 locus regulated 14 genes in cis and 857 genes in trans. In lung tumors of the same (A/J x C57BL/6)F4 mice, we found 1124 genes whose transcript levels associated with Nlung (FDR < 0.001). The expression levels of about a third of these genes (n = 401) were regulated by the genotype at the Pas1 locus. Pathway analysis of the sets of genes associated with Nlung and regulated by Pas1 revealed a set of 14 recurrently represented genes that are components or targets of the Ras-Erk and Pi3k-Akt signaling pathways. Altogether our results illustrate the architecture of germline control of gene expression in mouse lung cancer: they highlight the importance of Pas1 as a tumor-modifier locus, attribute to it a novel role as a major regulator of transcription in lung tumor nodules and strengthen the candidacy of the Kras gene as the effector of this locus. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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