Restoration of fibroblast growth factor receptor2 suppresses growth and tumorigenicity of malignant human prostate carcinoma PC-3 cells
Abstract
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. 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. 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. 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,...Continue Reading
References
Citations
2b or Not 2b: How Opposing FGF Receptor Splice Variants Are Blocking Progress in Precision Oncology.
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