Abstract
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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Differentiation
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Cell Proliferation
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Cell Survival
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Cell Transformation, Neoplastic
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Enzyme Activation
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Epithelial Cells / enzymology
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Epithelial Cells / metabolism*
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Epithelial Cells / pathology
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Epithelium / pathology
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Fibroblast Growth Factor 10 / metabolism*
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Genes, Dominant
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Male
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Mesoderm / pathology
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Mice
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Neoplasm Transplantation
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Organ Specificity
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Paracrine Communication*
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Prostatic Intraepithelial Neoplasia / enzymology
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Prostatic Intraepithelial Neoplasia / pathology
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Prostatic Neoplasms / enzymology
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Prostatic Neoplasms / pathology*
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Proto-Oncogene Proteins c-akt / metabolism
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Receptor, Fibroblast Growth Factor, Type 1 / metabolism
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Receptors, Androgen / metabolism*
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Regeneration
Substances
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Fgf10 protein, mouse
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Fibroblast Growth Factor 10
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Receptors, Androgen
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Receptor, Fibroblast Growth Factor, Type 1
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Proto-Oncogene Proteins c-akt