Seeding and Propagation of Untransformed Mouse Mammary Cells in the Lung

Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Science (Impact Factor: 33.61). 09/2008; 321(5897):1841-4. DOI: 10.1126/science.1161621
Source: PubMed


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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Available from: Nancy Du, Jan 14, 2014
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    • "Podsypanina et al. [33] used breast cancer metastasis model to study whether mammary gland cell in situ could be induced for metastasis when there was no oncogene-driven change in the primary site. Zeng et al. [34] evaluated the therapeutic effect by the combination of rapamycin and cyclophosphamide in MDA-MB-231 nude mice transplanted tumor model and used BLI to monitor tumor growth and metastasis. "
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    • "By turning on expression of a tetracycline-responsive transgene in the adult mouse, one can avoid potential complications caused by overexpression of the oncogene or by Cre recombinase-mediated removal of a LOXP-flanked cassette during development; likewise, expression can then be turned off after tumour formation to investigate the possibility of regression and recurrence. It should be noted that a TetON-PyV mT mouse strain has been reported which is sensitive to inducible mammary tumour progression in the presence of the MMTV-rtTA transgene; however, PyV mT is not coupled to Cre recombinase in this case [10]. "
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