Enhanced Paracrine FGF10 Expression Promotes Formation of Multifocal Prostate Adenocarcinoma and an Increase in Epithelial Androgen Receptor

Sanaz Memarzadeh; Li Xin; David J. Mulholland; Alka Mansukhani; Hong Wu; Michael A. Teitell; Owen N. Witte

doi:10.1016/j.ccr.2007.11.002

Enhanced Paracrine FGF10 Expression Promotes Formation of Multifocal Prostate Adenocarcinoma and an Increase in Epithelial Androgen Receptor

Sanaz Memarzadeh, Li Xin, David J. Mulholland, Alka Mansukhani, Hong Wu, Michael A. Teitell, Owen N. Witte

Research output: Contribution to journal › Article › peer-review

159 Scopus citations

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.

Original language	English
Pages (from-to)	572-585
Number of pages	14
Journal	Cancer Cell
Volume	12
Issue number	6
DOIs	https://doi.org/10.1016/j.ccr.2007.11.002
State	Published - 6 Dec 2007
Externally published	Yes

Keywords

CELLBIO
CELLCYCLE

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10.1016/j.ccr.2007.11.002

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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.",

keywords = "CELLBIO, CELLCYCLE",

author = "Sanaz Memarzadeh and Li Xin and Mulholland, {David J.} and Alka Mansukhani and Hong Wu and Teitell, {Michael A.} and Witte, {Owen N.}",

note = "Funding Information: We thank Ms. Barbara Anderson for her help in preparation of this manuscript and Ms. Donghui Cheng for her help in FACS sorting cells. S.M. has been supported by grants from NICHD-ABOG Reproductive Scientist Developmental Program 5K12HD00849-18 and NIH/National Cancer Institute, Clinical Scientist Training in Cancer Gene Medicine, K12-CA076905-09. L.X. is supported by a NIH Pathway to Independence Award 1K99CA125937 and a training grant from the California Institute for Regenerative Medicine. D.J.M. is funded by a National Institutes of Health (NIH) fellowship. H.W. is supported by NIH grant RO1 CA107166 and an Army Medical Research grant W81XWH-05-1-0542. M.A.T. is a Scholar of the Leukemia and Lymphoma Society and is supported by NIH grants R01CA90571 and R01CA107300, and California Institute for Regenerative Medicine (CIRM) grant RS1-00313. O.N.W. is an investigator of the Howard Hughes Medical Institute. ",

year = "2007",

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doi = "10.1016/j.ccr.2007.11.002",

language = "English",

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pages = "572--585",

journal = "Cancer Cell",

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T1 - Enhanced Paracrine FGF10 Expression Promotes Formation of Multifocal Prostate Adenocarcinoma and an Increase in Epithelial Androgen Receptor

AU - Memarzadeh, Sanaz

AU - Xin, Li

AU - Mulholland, David J.

AU - Mansukhani, Alka

AU - Wu, Hong

AU - Teitell, Michael A.

AU - Witte, Owen N.

N1 - Funding Information: We thank Ms. Barbara Anderson for her help in preparation of this manuscript and Ms. Donghui Cheng for her help in FACS sorting cells. S.M. has been supported by grants from NICHD-ABOG Reproductive Scientist Developmental Program 5K12HD00849-18 and NIH/National Cancer Institute, Clinical Scientist Training in Cancer Gene Medicine, K12-CA076905-09. L.X. is supported by a NIH Pathway to Independence Award 1K99CA125937 and a training grant from the California Institute for Regenerative Medicine. D.J.M. is funded by a National Institutes of Health (NIH) fellowship. H.W. is supported by NIH grant RO1 CA107166 and an Army Medical Research grant W81XWH-05-1-0542. M.A.T. is a Scholar of the Leukemia and Lymphoma Society and is supported by NIH grants R01CA90571 and R01CA107300, and California Institute for Regenerative Medicine (CIRM) grant RS1-00313. O.N.W. is an investigator of the Howard Hughes Medical Institute.

PY - 2007/12/6

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N2 - 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.

AB - 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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Enhanced Paracrine FGF10 Expression Promotes Formation of Multifocal Prostate Adenocarcinoma and an Increase in Epithelial Androgen Receptor

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