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


RESULTS
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
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.
Gibbons
Don L
DL
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
Lin
Wei
W
Creighton
Chad J
CJ
Zheng
Shuling
S
Berel
Dror
D
Yang
Yanan
Y
Raso
Maria Gabriela
MG
Liu
Diane D
DD
Wistuba
Ignacio I
II
Lozano
Guillermina
G
Kurie
Jonathan M
JM
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D011905:Genes, ras / Q000235:genetics; D020022:Genetic Predisposition to Disease; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D020125:Mutation, Missense; D009362:Neoplasm Metastasis / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016159:Tumor Suppressor Protein p53