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Vol. 15, No. 24, pp. 3243-3248, December 15, 2001
1 Department of Biology and 2 Howard Hughes
Medical Institute, Massachusetts Institute of Technology, Cambridge,
Massachusetts 02139, USA; 3 Dana-Farber Cancer Institute,
Division of Adult Oncology, Boston, Massachusetts 02115, USA;
4 Department of Pathology, Tufts University School of
Medicine and Veterinary Medicine, Boston, Massachusetts 02111, USA
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.
[Key Words: K-ras; lung cancer; mouse models; Cre-loxP]
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