title: Enhanced paracrine FGF10 expression promotes formation of multifocal prostate adenocarcinoma and an increase in epithelial androgen receptor.
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.
authors: Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Sanaz
authors: S
authors: Memarzadeh
authors: Li
authors: L
authors: Xin
authors: David J
authors: DJ
authors: Mulholland
authors: Alka
authors: A
authors: Mansukhani
authors: Hong
authors: H
authors: Wu
authors: Michael A
authors: MA
authors: Teitell
authors: Owen N
authors: ON
authors: Witte
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism*; D005799:Genes, Dominant; D008297:Male; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D009928:Organ Specificity; D019899:Paracrine Communication; D019048:Prostatic Intraepithelial Neoplasia / Q000201:enzymology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D012038:Regeneration
chemical_list: C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D011944:Receptors, Androgen; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051057:Proto-Oncogene Proteins c-akt