Enhanced paracrine FGF10 expression promotes formation of multifocal prostate adenocarcinoma and an increase in epithelial androgen receptor.
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.
Memarzadeh
Sanaz
S
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Xin
Li
L
Mulholland
David J
DJ
Mansukhani
Alka
A
Wu
Hong
H
Teitell
Michael A
MA
Witte
Owen N
ON
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
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