Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras.
Adenocarcinoma of the lung is the most common form of lung cancer, but the cell of origin and the stages of progression of this tumor type are not well understood. We have developed a new model of lung adenocarcinoma in mice harboring a conditionally activatable allele of oncogenic K-ras. Here we show that the use of a recombinant adenovirus expressing Cre recombinase (AdenoCre) to induce K-ras G12D expression in the lungs of mice allows control of the timing and multiplicity of tumor initiation. Through the ability to synchronize tumor initiation in these mice, we have been able to characterize the stages of tumor progression. Of particular significance, this system has led to the identification of a new cell type contributing to the development of pulmonary adenocarcinoma.
Jackson
E L
EL
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Willis
N
N
Mercer
K
K
Bronson
R T
RT
Crowley
D
D
Montoya
R
R
Jacks
T
T
Tuveson
D A
DA
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D003062:Codon; D018450:Disease Progression; D015870:Gene Expression; D011905:Genes, ras / Q000235:genetics*; D007124:Immunoenzyme Techniques; D019426:Integrases / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009154:Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D013997:Time Factors; D014764:Viral Proteins / Q000378:metabolism
D003062:Codon; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases; D016283:Proto-Oncogene Proteins p21(ras)