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Inducible FGFR-1 activation leads to irreversible prostate adenocarcinoma and an epithelial-to-mesenchymal transition.

Authors: Acevedo, VD  Gangula, RD  Freeman, KW  Li, R  Zhang, Y  Wang, F  Ayala, GE  Peterson, LE  Ittmann, M  Spencer, DM 
Citation: Acevedo VD, etal., Cancer Cell. 2007 Dec;12(6):559-71.
Pubmed: (View Article at PubMed) PMID:18068632
DOI: Full-text: DOI:10.1016/j.ccr.2007.11.004

Fibroblast Growth Factor Receptor-1 (FGFR1) is commonly overexpressed in advanced prostate cancer (PCa). To investigate causality, we utilized an inducible FGFR1 (iFGFR1) prostate mouse model. Activation of iFGFR1 with chemical inducers of dimerization (CID) led to highly synchronous, step-wise progression to adenocarcinoma that is linked to an epithelial-to-mesenchymal transition (EMT). iFGFR1 inactivation by CID withdrawal led to full reversion of prostatic intraepithelial neoplasia, whereas PCa lesions became iFGFR1-independent. Gene expression profiling at distinct stages of tumor progression revealed an increase in EMT-associated Sox9 and changes in the Wnt signaling pathway, including Fzd4, which was validated in human PCa. The iFGFR1 model clearly implicates FGFR1 in PCa progression and demonstrates how CID-inducible models can help evaluate candidate molecules in tumor progression and maintenance.

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CRRD Object Information
CRRD ID: 2298702
Created: 2008-07-15
Species: All species
Last Modified: 2008-07-15
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.