ETV6-NTRK3 Fusion Oncogene Initiates Breast Cancer from Committed Mammary Progenitors via Activation of AP1 Complex

Zhe Li, Cristina E. Tognon, Frank J. Godinho, Laura Yasaitis, Hanno Hock, Jason I. Herschkowitz, Chris L. Lannon, Eunah Cho, Seong Jin Kim, Roderick T. Bronson, Charles M. Perou, Poul H. Sorensen, Stuart H. Orkin

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

To better understand the cellular origin of breast cancer, we developed a mouse model that recapitulates expression of the ETV6-NTRK3 (EN) fusion oncoprotein, the product of the t(12;15)(p13;q25) translocation characteristic of human secretory breast carcinoma. Activation of EN expression in mammary tissues by Wap-Cre leads to fully penetrant, multifocal malignant breast cancer with short latency. We provide genetic evidence that, in nulliparous Wap-Cre;EN females, committed alveolar bipotent or CD61+ luminal progenitors are targets of tumorigenesis. Furthermore, EN transforms these otherwise transient progenitors through activation of the AP1 complex. Given the increasing relevance of chromosomal translocations in epithelial cancers, such mice serve as a paradigm for the study of their genetic pathogenesis and cellular origins, and generation of preclinical models.

Original languageEnglish (US)
Pages (from-to)542-558
Number of pages17
JournalCancer Cell
Volume12
Issue number6
DOIs
StatePublished - Dec 6 2007
Externally publishedYes

Keywords

  • CELLCYCLE
  • STEMCELL

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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