Author/Authors :
Li، نويسنده , , Zhe and Tognon، نويسنده , , Cristina E. and Godinho، نويسنده , , Frank J. and Yasaitis، نويسنده , , Laura and Hock، نويسنده , , Hanno and Herschkowitz، نويسنده , , Jason I. and Lannon، نويسنده , , Chris L. and Cho، نويسنده , , Eunah and Kim، نويسنده , , Seong-Jin and Bronson، نويسنده , , Roderick T. and Perou، نويسنده , , Charles M. and Sorensen، نويسنده , , Poul H. and Orkin، نويسنده , , Stuart H.، نويسنده ,
Abstract :
Summary
ter 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.
