ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex.

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.
Authors	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
Journal	Cancer cell (Cancer Cell) Vol. 12 Issue 6 Pg. 542-58 (Dec 2007) ISSN: 1535-6108 [Print] United States
PMID	18068631 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	CD24 Antigen ETS translocation variant 6 protein ETV6-NTRK3 fusion protein, mouse Oncogene Proteins, Fusion Proto-Oncogene Proteins c-ets Proto-Oncogene Proteins c-jun Repressor Proteins Transcription Factor AP-1 Cre recombinase Integrases
Topics	Alleles Animals Breast Neoplasms (genetics, pathology) CD24 Antigen (metabolism) Cell Transformation, Neoplastic Epithelial Cells (metabolism, pathology) Female Genes, Dominant Humans Integrases (metabolism) Mammary Glands, Animal (pathology) Mammary Neoplasms, Animal (pathology) Mice Multigene Family Neoplastic Stem Cells (pathology) Oncogene Proteins, Fusion (metabolism) Parity Penetrance Pregnancy Proto-Oncogene Proteins c-ets (metabolism) Proto-Oncogene Proteins c-jun (metabolism) Repressor Proteins (metabolism) Transcription Factor AP-1 (metabolism)

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