Inducible FGFR-1 Activation Leads to Irreversible Prostate Adenocarcinoma and an Epithelial-to-Mesenchymal Transition

Victor D. Acevedo, Rama D. Gangula, Kevin W. Freeman, Rile Li, Youngyou Zhang, Fen Wang, Gustavo E. Ayala, Leif E. Peterson, Michael Ittmann, David M. Spencer

Research output: Contribution to journalArticle

213 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)559-571
Number of pages13
JournalCancer Cell
Volume12
Issue number6
DOIs
StatePublished - Dec 6 2007

Keywords

  • CELLBIO
  • CELLCYCLE

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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