Seeding and Propagation of Untransformed Mouse Mammary Cells in the Lung

Science. 2008 Sep 26;321(5897):1841-4. doi: 10.1126/science.1161621. Epub 2008 Aug 28.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / pathology
  • Adenocarcinoma / secondary
  • Animals
  • Antigens, Polyomavirus Transforming / genetics
  • Cell Proliferation
  • Cell Survival
  • Cell Transformation, Neoplastic
  • Epithelial Cells / cytology*
  • Gene Expression Regulation, Neoplastic
  • Genes, myc
  • Genes, ras
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary*
  • Mammary Glands, Animal / cytology*
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Transgenic
  • Neoplasm Metastasis*
  • Neoplasm Seeding*
  • Neoplastic Cells, Circulating
  • Oncogenes*
  • Transgenes

Substances

  • Antigens, Polyomavirus Transforming