Restoration of fibroblast growth factor receptor2 suppresses growth and tumorigenicity of malignant human prostate carcinoma PC-3 cells.
BACKGROUND
Fibroblast growth factors (FGFs) and their receptors (FGFRs) expedite stromal-epithelial communication in development and homeostasis of the human prostate. Loss of resident epithelial cell FGFR2IIIb that responds to stromal FGF7 and FGF10 accompanies malignant progression of both model animal and human prostate tumors.


METHODS
We examined whether restoration of FGFR2IIIb by transfection in the malignant human prostate tumor PC-3 cell line restored cellular properties associated with less malignant tumors. Cell proliferation, apoptosis, and tumor cell implants were used to monitor malignant properties. Activity of FGFR2IIIb was assessed by immunoblot of FRS2 and p44/42 MAP kinase. Immunochemical analysis of pancytokeratin and lactoferrin expression was utilized to assess changes in cellular differentiation.


RESULTS
Expression of FGFR2IIIb in PC-3 cells by transfection resulted in growth suppression in vitro and reduced tumor formation in vivo concurrent with increased cellular differentiation and apoptosis.


CONCLUSIONS
The results indicate that restoration of FGFR2IIIb to the malignant human prostate epithelial cell prototype PC-3 restores properties associated with nonmalignant tumors and normal cells. This further suggests that epithelial cell resident, homeostasis-promoting FGFR2 may be involved in suppression of malignancy and that restoration may be a candidate for gene therapy of hormone-refractory prostate cancer.
Yasumoto
Hiroaki
H
Department of Urology, Division of Frontier Medical Science Programs for Biomedical Research, Graduate School of Biomedical Sciences Hiroshima University, Hiroshima, Japan.
Matsubara
Akio
A
Mutaguchi
Kazuaki
K
Usui
Tsuguru
T
McKeehan
Wallace L
WL
D017209:Apoptosis; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor / Q000166:cytology / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology; D014162:Transfection
D017468:Receptors, Fibroblast Growth Factor; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D020928:Mitogen-Activated Protein Kinases