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Published Online August 28, 2008
Science DOI: 10.1126/science.1161621

Reports

Submitted on June 10, 2008
Accepted on August 11, 2008

Seeding and Propagation of Untransformed Mouse Mammary Cells in the Lung

Katrina Podsypanina 1*, Yi-Chieh Nancy Du 1, Martin Jechlinger 1, Levi J. Beverly 1, Dolores Hambardzumyan 1, Harold Varmus 1

1 Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

* To whom correspondence should be addressed.
Katrina Podsypanina , E-mail: podsypak{at}mskcc.org

Acquisition of metastatic ability by tumor cells is considered a late event in the evolution of malignant tumors. Here we report that untransformed mouse mammary cells, engineered to express inducible oncogenic transgenes: MYC and KrasD12, or polyoma middle T, and introduced into the systemic circulation of a mouse, can bypass transformation at the primary site and develop into metastatic pulmonary lesions upon immediate or delayed oncogene induction. Therefore, previously untransformed mammary cells may establish residence in the lung once they have entered the bloodstream, and may assume malignant growth upon oncogene activation. Mammary cells lacking oncogenic transgenes displayed a similar capacity for long-term residence in the lungs but did not form ectopic tumors.


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