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Conditional activation of Neu in the mammary epithelium of transgenic mice results in reversible pulmonary metastasis.

To determine the impact of tumor progression on the reversibility of Neu-induced tumorigenesis, we have used the tetracycline regulatory system to conditionally express activated Neu in the mammary epithelium of transgenic mice. When induced with doxycycline, bitransgenic MMTV-rtTA/TetO-NeuNT mice develop multiple invasive mammary carcinomas, essentially all of which regress to a clinically undetectable state following transgene deinduction. This demonstrates that Neu-initiated tumorigenesis is reversible. Strikingly, extensive lung metastases arising from Neu-induced mammary tumors also rapidly and fully regress following the abrogation of Neu expression. However, despite the near universal dependence of both primary tumors and metastases on Neu transgene expression, most animals bearing fully regressed Neu-induced tumors ultimately develop recurrent tumors that have progressed to a Neu-independent state.

Pubmed ID: 12498714

Authors

  • Moody SE
  • Sarkisian CJ
  • Hahn KT
  • Gunther EJ
  • Pickup S
  • Dugan KD
  • Innocent N
  • Cardiff RD
  • Schnall MD
  • Chodosh LA

Journal

Cancer cell

Publication Data

December 24, 2002

Associated Grants

  • Agency: NCI NIH HHS, Id: CA16520
  • Agency: NCI NIH HHS, Id: CA92190
  • Agency: NCI NIH HHS, Id: CA93719
  • Agency: NCI NIH HHS, Id: CA94393
  • Agency: NCI NIH HHS, Id: K08 CA79682

Mesh Terms

  • Adenocarcinoma
  • Animals
  • Blotting, Northern
  • Cell Transformation, Neoplastic
  • Down-Regulation
  • Doxycycline
  • Epithelium
  • Female
  • Gene Expression Regulation
  • Genes, erbB-2
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Lung Neoplasms
  • Magnetic Resonance Imaging
  • Mammary Glands, Animal
  • Mammary Neoplasms, Experimental
  • Mice
  • Mice, Transgenic
  • Models, Animal
  • Neoplasm Transplantation
  • Remission Induction
  • Transgenes