Enhanced paracrine FGF10 expression promotes formation of multifocal prostate adenocarcinoma and an increase in epithelial androgen receptor

Cancer Cell. 2007 Dec;12(6):572-85. doi: 10.1016/j.ccr.2007.11.002.


Enhanced mesenchymal expression of FGF10 led to the formation of multifocal PIN or prostate cancer. Inhibition of epithelial FGFR1 signaling using DN FGFR1 led to reversal of the cancer phenotype. A subset of the FGF10-induced carcinoma was serially transplantable. Paracrine FGF10 led to an increase in epithelial androgen receptor and synergized with cell-autonomous activated AKT. Our observations indicate that stromal FGF10 expression may facilitate the multifocal histology observed in prostate adenocarcinoma and suggest the FGF10/FGFR1 axis as a potential therapeutic target in treating hormone-sensitive or refractory prostate cancer. We also show that transient exposure to a paracrine growth factor may be sufficient for the initiation of oncogenic transformation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival
  • Cell Transformation, Neoplastic
  • Enzyme Activation
  • Epithelial Cells / enzymology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Epithelium / pathology
  • Fibroblast Growth Factor 10 / metabolism*
  • Genes, Dominant
  • Male
  • Mesoderm / pathology
  • Mice
  • Neoplasm Transplantation
  • Organ Specificity
  • Paracrine Communication*
  • Prostatic Intraepithelial Neoplasia / enzymology
  • Prostatic Intraepithelial Neoplasia / pathology
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / pathology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Receptors, Androgen / metabolism*
  • Regeneration


  • Fgf10 protein, mouse
  • Fibroblast Growth Factor 10
  • Receptors, Androgen
  • Receptor, Fibroblast Growth Factor, Type 1
  • Proto-Oncogene Proteins c-akt