BASIC RESEARCH OF NEW GENE THERAPY FOR PROSTATE CANCER WITH GROWTH FACTOR RECEPTOR

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We have been investigating the potential roles of fibroblast growth factor receptors (FGFRs) in growth control of prostate tumors. Consequently we have recently found that hormone-dependent prostate tumor cells express FGFR2IIIb which mediates response to stromal-derived growth regulator FGF-7, while they lose the expression of FGFR2IIIb during progression from hormone-dependent to hormone-independent and escape the growth regulation by FGF-7. Instead the hormone-independent prostate tumor cells express FGFR1 and acquire autonomy. The results indicate that both restoration of FGFR2IIIb and deactivation of FGFR1 may result in a treatment of hormone-refractory prostate cancer. Thus, we induced the expression of FGFR2IIIb in hormone-independent rat prostate tumor cells by transfection. As a result, the transfected cells regained communication with stroma and not only showed reduced population growth rates, but also recovered cytokeratin expression and gland-like morphology specific to hormone-dependent tumors. We also transfected hormone-independent rat prostate tumor cells with kinase-defective FGFR1 to deactivate the endogenous FGFR1 by dominant-negative effect. As a result, in vivo growth of the transfected cells was similar to that of FGFR2IIIb-introduced cells.