Seeding and Propagation of Untransformed Mouse Mammary Cells in the Lung

American Association for the Advancement of Science (AAAS) - Tập 321 Số 5897 - Trang 1841-1844 - 2008
Katrina Podsypanina1, Yi-Chieh Nancy Du1, Martin Jechlinger1, Levi J. Beverly1, Dolores Hambardzumyan1, Harold Varmus1
1Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Tóm tắt

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.

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Tài liệu tham khảo

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We thank M. A. Melnick G. Sanchez A. Giannakou and J. Demers for expert handling of the mouse colony; L. Chodosh for providing MMTV-rtTA transgenic mice; D. Felsher and J. M. Bishop for providing TetO-MYC transgenic mice; A. Olshen for assistance with statistical analysis; and L. K. Tan for assistance with histological analysis. Supported in part by awards from NIH (K01 CA118731 to K.P. P01 CA94060 to H.V. and R24 CA83084 and P30-CA 08748 which provides partial support for core facilities used in conducting this investigation) the Martell Foundation (to H.V.) and the U.S. Department of Defense (W81XWH-05-1-0220 to M.J.).

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American Association for the Advancement of Science (AAAS)

Tập 321 Số 5897

1841-1844

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