ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex.
Document Type
Article
Publication Date
2007
Keywords
Animals, Antigens-CD24, Breast-Neoplasms, Cell-Transformation-Neoplastic, Epithelial-Cells, Female, Genes-Dominant, Humans, Integrases, Mammary-Glands-Animal, Mammary-Neoplasms-Animal, Mice, Multigene-Family, Neoplastic-Stem-Cells, Oncogene-Proteins-Fusion, Parity, Penetrance, Pregnancy, Proto-Oncogene-Proteins-c-ets, Proto-Oncogene-Proteins-c-jun, Repressor-Proteins, Transcription-Factor-AP-1
First Page
542
Last Page
558
JAX Source
Cancer Cell 2007 Dec; 12(6):542-58.
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.
Recommended Citation
Li Z,
Tognon CE,
Godinho FJ,
Yasaitis L,
Hock H,
Herschkowitz JI,
Lannon CL,
Cho E,
Kim SJ,
Bronson RT,
Perou CM,
Sorensen PH,
Orkin SH.
ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex. Cancer Cell 2007 Dec; 12(6):542-58.