Seeding and Propagation of Untransformed Mouse Mammary Cells in the Lung

• DOI: 10.1126/science.1161621
• Publication Date: 2008-08-29T01:41:20Z
• Authors: Katrina Podsypanina; Yi-Chieh Nancy Du; Martin Jechlinger; Levi J. Beverly; Dolores Hambardzu...; Harold Varmus
• Keywords: Lung Neoplasms; Cell Survival; Antigens, Polyomavirus Transforming; Genes, myc; Mammary Neoplasms, Experimental; Epithelial Cells; Mice, Transgenic; Oncogenes; Adenocarcinoma; Neoplastic Cells, Circulating; Gene Expression Regulation, Neoplastic; Mice; Cell Transformation, Neoplastic; Genes, ras; Mammary Glands, Animal; Neoplasm Seeding; Animals; Transgenes; Neoplasm Metastasis; Cell Proliferation

The acquisition of metastatic ability by tumor cells is considered a late event in the evolution of malignant tumors. We report that untransformed mouse mammary cells that have been engineered to express the inducible oncogenic transgenes MYC and Kras D12 , 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.