Expression signatures of metastatic capacity in a genetic mouse model of lung adenocarcinoma

PLoS One. 2009;4(4):e5401. doi: 10.1371/journal.pone.0005401. Epub 2009 Apr 30.

Abstract

Background: Non-small cell lung cancer (NSCLC) is the foremost cause of cancer-related death in Western countries, which is due partly to the propensity of NSCLC cells to metastasize. The biologic basis for NSCLC metastasis is not well understood.

Methodology/principal findings: Here we addressed this deficiency by transcriptionally profiling tumors from a genetic mouse model of human lung adenocarcinoma that develops metastatic disease owing to the expression of K-ras(G12D) and p53(R172H). We identified 2,209 genes that were differentially expressed in distant metastases relative to matched lung tumors. Mining of publicly available data bases revealed this expression signature in a subset of NSCLC patients who had a poorer prognosis than those without the signature.

Conclusions/significance: These findings provide evidence that K-ras(G12D); p53(R172H) mice recapitulate features of human NSCLC metastasis and will provide a useful platform on which to study the biologic basis for lung adenocarcinoma metastasis and its prevention by novel agents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease Models, Animal*
  • Gene Expression Profiling
  • Genes, ras / genetics
  • Genetic Predisposition to Disease
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Mice
  • Mutation, Missense*
  • Neoplasm Metastasis / genetics*
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Tumor Suppressor Protein p53