|
| Status |
Public on Mar 01, 2010 |
| Title |
FGF Receptor and Wnt-1 Signaling Cooperate in Mammary Tumorigenesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The fibroblast growth factor pathway is known to cooperate with the highly oncogenic Wnt/beta-catenin pathway in mouse models of breast cancer. To investigate the mechanisms involved in this cooperativity, we utilized MMTV-driven transgenic mouse lines expressing a drug-inducible model for FGF Receptor signaling (iFGFR) crossed with the previously characterized MMTV-Wnt-1 mouse model. In these bigenic mice, both iFGFR1 and iFGFR2 activation resulted in a dramatic enhancement of mammary tumorigenesis. Tumor microarray analysis identified no transcriptional enhancement of Wnt/beta-catenin targets, however, identified a protein translational gene signature that also correlated with elevated FGFR1 and FGFR2 expression in several human breast cancer data sets. Additionally, iFGFR1 activation resulted in enhanced polysome recruitment and a marked increase in protein expression of several different Wnt/beta-catenin target oncogenes. Rapid FGFR-induced ERK activation and phosphorylation of key translation regulators was observed both in vivo in the transgenic mouse model, and in human breast cancer cell lines treated with exogenous FGF. These studies suggest that translational regulation is a key rate-limiting step required for oncogenic cooperativity between the Wnt and FGF pathways.
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| Overall design |
reference X sample
|
| |
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| Contributor(s) |
Pond AC, Herschkowitz JI, Perou CM |
| Citation(s) |
20501844 |
| |
| Submission date |
Sep 01, 2009 |
| Last update date |
Jul 17, 2015 |
| Contact name |
Charles M. Perou |
| E-mail(s) |
[email protected]
|
| 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 |
| |
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| Platforms (1) |
| GPL2881 |
Agilent-013326 Mouse Oligo Microarray (V2) G4121B (Feature Number version) |
|
| Samples (18)
|
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| Relations |
| BioProject |
PRJNA120047 |
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