 |
 |
GEO help: Mouse over screen elements for information. |
|
| 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 |
| GSM237859 |
MIXED_Wap_Cre_ETV6_NTRK3_CR115_ORKIN |
| GSM237860 |
MIXED_Wap_Cre_ETV6_NTRK3_CR90-1_ORKIN |
| GSM237861 |
MIXED_Wap_Cre_ETV6_NTRK3_D14T1_ORKIN |
| GSM237862 |
MIXED_Wap_Cre_ETV6_NTRK3_D14T2_ORKIN |
| GSM237863 |
MIXED_Wap_Cre_ETV6_NTRK3_D203T1_ORKIN |
| GSM237864 |
MIXED_Wap_Cre_ETV6_NTRK3_D254T1_ORKIN |
| GSM237865 |
MIXED_Wap_Cre_ETV6_NTRK3_D279T1_ORKIN |
| GSM237866 |
MIXED_Wap_Cre_ETV6_NTRK3_D481_ORKIN |
| GSM237867 |
MIXED_Wap_Cre_ETV6_NTRK3_E93T1_ORKIN |
|
| Relations |
| BioProject |
PRJNA103029 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE9343_RAW.tar |
3.3 Mb |
(http)(custom) |
TAR |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...