Basic research on novel therapy for hormone-refractory prostate cancer with tyrosine kinase

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We induced, by transfection, fibroblast growth factor receptor 2 Illb (FGFR2IIIb) kinase in hormone-independent human prostate cancer cell line, PC-3 cells. Consequently, the transfected PC-3 cells fell in a state of strong apoptosis and showed significantly reduced population growth rates in vitro and in vivo. In addition, the growth suppression was significantly accelerated by the addition of specific *igand for FGFR2IIIb, FGF-7. The expression levels of cytokeratin and lactoferrin, which are indicators for cell differentiation, markedly increased in the transfected PC-3 cells. These results indicate that the FGFR2IIIb has not only a growth suppressing but also differentiation inducing properties for hormone-independent prostate cancer cells.In the present study, The FGFR2IIIb signaling pathway was also analyzed by Western blotting. As a result, the FRS2 signal intensity of transfected PC-3 cells was much stronger than that of control cells. After stimulation with FGF-7, FRS2 was strongly activated in transfected PC-3, but not control, cells. Also, after stimulation with FGF-1 and FGF-7, phosphorylation of p44/42 MAP kinase was detected in transfected PC-3, but not control, cells. These results indicate that the FGFR2IIIb signals in transfected PC-3 cells are closely associated with phosphorylation of FRS2 and MAP kinase. Thus the growth suppressing and differentiation inducing properties of FGFR2IIIb were considered to be induced by the activation of FRS2 and MAP kinase.