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

Susan E. Moody, Christopher J. Sarkisian, Kristina T. Hahn, Edward J. Gunther, Steven Pickup, Katherine D. Dugan, Nathalie Innocent, Robert D. Cardiff, Mitchell D. Schnall, Lewis A. Chodosh

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292 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)451-461
Number of pages11
JournalCancer Cell
Volume2
Issue number6
DOIs
StatePublished - Dec 2002

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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