Enhanced Paracrine FGF10 Expression Promotes Formation of Multifocal Prostate Adenocarcinoma and an Increase in Epithelial Androgen Receptor
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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.
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Expression of FGF10 by urogenital mesenchymal cells results in the induction of multifocal prostatic adenocarcinoma in epithelial cells.
“For example, expression of fibroblast growth factor 10 (FGF10) by urogenital mesenchymal cells results in the induction of multifocal prostatic adenocarcinoma in epithelial cells.52”
From Paracrine roles of cellular senescence in promoting tumourigenesis (2018) · cites this paper as [52]
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- Authors
- Memarzadeh, S., Xin, L., Mulholland, D. J., Mansukhani, A., Wu, H., Teitell, M. A., & Witte, O. N.
- Affiliations
- University of California, Los Angeles (US)
- NYU Langone Health (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Witte, Owen N.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 12
- Issue
- 6
- Pages
- 572-585
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC2931420
- OpenAlex
- W2011566841
- Cited by
- 201
- References
- 62
- Citations by year
- 2025: 5 · 2024: 10 · 2023: 8 · 2022: 3 · 2021: 10 · 2020: 7 · 2019: 7 · 2018: 11 · 2017: 8 · 2016: 7 · 2015: 20 · 2014: 17 · 2013: 22 · 2012: 9
- FWCI
- 11.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (R01CA107300, K12CA076905, K12-CA076905-09, R01CA107166, R01CA090571, K99CA125937)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (5K12HD00849-18, K12HD000849)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Diagnosis and Treatment
- Keywords
- FGF10, FGFR1, prostate adenocarcinoma, multifocal prostate cancer, paracrine signaling, mesenchymal stroma, androgen receptor, Akt activation, prostatic intraepithelial neoplasia, oncogenic transformation, hormone-sensitive prostate cancer, therapeutic target
- MeSH terms
- Animals, Cell Differentiation, Cell Survival, Cell Transformation, Neoplastic, Enzyme Activation, Epithelial Cells, Epithelium, Genes, Dominant, Male, Mesoderm, Neoplasm Transplantation, Organ Specificity, Prostatic Neoplasms, Receptors, Androgen, Regeneration, Prostatic Intraepithelial Neoplasia, Paracrine Communication, Cell Proliferation, Proto-Oncogene Proteins c-akt, Mice, Receptor, Fibroblast Growth Factor, Type 1, Fibroblast Growth Factor 10
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