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Series GSE9343 Query DataSets for GSE9343
Status Public on Apr 07, 2008
Title ETV6-NTRK3 fusion oncogene initiates breast cancer from committed alveolar progenitors via activation of AP1 complex
Organism Mus musculus
Experiment type Expression profiling by array
Summary For the largest class of human tumors, those of epithelial origin, little is known about their initiating genetic hits or cells of origin. Whether tissue stem cells or more committed progenitors are targets for transformation is also uncertain. Experience in hematopoietic malignancies and sarcomas teaches that recurrent chromosomal translocations represent initiating oncogenic events. To develop a system in which epithelial tumorigenesis can be assessed from the initial event to frank malignancy, we have generated mice that conditionally express the Etv6-NTRK3 (EN) fusion oncoprotein, the product of the t(12;15)(p13;q25) translocation characteristic of one form of human breast cancer. Activation of EN expression in mammary tissues by Whey acidic protein (Wap) promoter-driven Cre leads to fully penetrant, multifocal malignant breast cancer with short latency. We provide genetic evidence that committed, bipotent or CD61+ luminal alveolar progenitors, can be targets of tumorigenesis. Furthermore, EN transforms these otherwise transient progenitors through the AP1 complex. Our model supports the existence of an epithelial cell hierarchy in both normal mammary glands and malignancy. To our knowledge, this is the first murine model of human epithelial cancer based on a recurrent chromosomal translocation. Given 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 novel preclinical models.
Keywords: Reference X Sample
 
Overall design Reference X Sample
 
Contributor(s) Li Z, Togon C, Godinho F, Yasaitis L, Hock H, Herschkowitz J, lannon C, Cho E, Kim S, Bronson R, Perou C, Sorensen P, Orkin S
Citation(s) 18068631
Submission date Oct 16, 2007
Last update date Jul 17, 2015
Contact name Charles M. Perou
E-mail(s) cperou@med.unc.edu
Organization name University of North Carolina at Chapel Hill
Department Professor of Genetics, and Pathology & Laboratory Medicine; Lineberger Comprehensive Cancer Center
Street address 12-044 Lineberger Comprehensive Cancer Center CB# 7295
City Chapel Hill
State/province NC
ZIP/Postal code 27599-7264
Country USA
 
Platforms (1)
GPL2881 Agilent-013326 Mouse Oligo Microarray (V2) G4121B (Feature Number version)
Samples (12)
GSM237856 MIXED_Wap_Cre_ETV6_NTRK3_C117T1_ORKIN
GSM237857 MIXED_Wap_Cre_ETV6_NTRK3_C393T1_ORKIN
GSM237858 MIXED_Wap_Cre_ETV6_NTRK3_C395T5_ORKIN
Relations
BioProject PRJNA103029

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE9343_RAW.tar 3.3 Mb (http)(custom) TAR
Processed data included within Sample table

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