Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras

  1. Erica L. Jackson1,
  2. Nicholas Willis1,
  3. Kim Mercer1,2,
  4. Roderick T. Bronson4,
  5. Denise Crowley1,2,
  6. Raymond Montoya1,
  7. Tyler Jacks1,2,5, and
  8. David A. Tuveson1,2,3
  1. 1Department of Biology and 2Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; 3Dana-Farber Cancer Institute, Division of Adult Oncology, Boston, Massachusetts 02115, USA; 4Department of Pathology, Tufts University School of Medicine and Veterinary Medicine, Boston, Massachusetts 02111, USA

Abstract

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.

Keywords

Footnotes

  • 5 Corresponding author.

  • E-MAIL tjacks{at}mit.edu; FAX (617) 253-9863.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.943001.

    • Received September 4, 2001.
    • Accepted October 24, 2001.
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