Transcriptomics

Dataset Information

27

FGF Receptor and Wnt-1 Signaling Cooperate in Mammary Tumorigenesis


ABSTRACT: 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. Overall design: reference X sample

INSTRUMENT(S): Agilent-013326 Mouse Oligo Microarray (V2) G4121B (Feature Number version)

ORGANISM(S): Mus musculus  

SUBMITTER: Charles M. Perou  

PROVIDER: GSE17916 | GEO | 2010-03-01

SECONDARY ACCESSION(S): PRJNA120047

REPOSITORIES: GEO

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