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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
Cancer cell | 2007

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.

Pubmed ID: 18068631

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: U01 CA105423-03
  • Agency: NCI NIH HHS, United States
    Id: U01 CA105423
  • Agency: NCI NIH HHS, United States
    Id: R01 CA101227
  • Agency: NCI NIH HHS, United States
    Id: N01CN43308
  • Agency: NCI NIH HHS, United States
    Id: N01-CN43308
  • Agency: NCI NIH HHS, United States
    Id: R01-CA-101227
  • Agency: NCI NIH HHS, United States
    Id: U01 CA105423-04

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Gene Set Enrichment Analysis (tool)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

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dChip Software (tool)

RRID:SCR_013504

Software for analysis and visualization of gene expression and SNP microarrays.

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