@article{224a462596d540039a15ee7315e1f3c2,
title = "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.",
keywords = "CELLCYCLE, STEMCELL",
author = "Zhe Li and Tognon, {Cristina E.} and Godinho, {Frank J.} and Laura Yasaitis and Hanno Hock and Herschkowitz, {Jason I.} and Lannon, {Chris L.} and Eunah Cho and Kim, {Seong Jin} and Bronson, {Roderick T.} and Perou, {Charles M.} and Sorensen, {Poul H.} and Orkin, {Stuart H.}",
note = "Funding Information: We thank Dr. Yuko Fujiwara, Aimee Williams, and Nicole Stokes for help with transgenic mice; Carol Browne for assistance with ES cell targeting; Melanie Hamblen for general support; Grigoriy Losyev for cell sorting; Dr. Leonard Zon for discussion; Dr. Tim Triche for help with microarray of 3T3 cells. This work was supported by grants to S.H.O. from the NCI Mouse Models of Human Cancer Consortium and from the Department of Defense, by grants to P.H.S. from the Canadian Institutes for Health Research (CIHR), by funds to C.M.P. from NCI (RO1-CA-101227-01) and HHSN-261200433008C (N01-CN43308), and by a K99 Pathway-to-Independence award to Z.L. from NCI. S.H.O. is an Investigator of the Howard Hughes Medical Institute. C.E.T. was supported by a ReThink Breast Cancer Career Development Award. ",
year = "2007",
month = dec,
day = "6",
doi = "10.1016/j.ccr.2007.11.012",
language = "English",
volume = "12",
pages = "542--558",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",
}