Hormone refractory prostate cancer and fibroblast growth factor receptor
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In prostate cancer, a distinct series of alterations in the fibroblast growth factor (FGF) family occurs during the progression from a hormone-dependent to independent state that disrupts communication between stroma and epithelium and results in autonomy of cancer cells. Changes include (i) loss of FGFR2lllb, which binds stromal-derived FGF-7, which promotes growth, growth limitation and differentiation and (ii) activation of FGFR1, the expression of which is normally limited to stroma, along with activation of FGFs that act on FGFR1 in an autocrine manner. Transfection of the FGFR2lllb isoform into hormone-independent prostate cancer cells not only causes growth inhibition, but also induces differentiation. However, introduction of FGFR1 by transfection in hormone-dependent prostate cancer cells accelerates their progression to malignancy. These results suggest distinct targets for therapy aimed at both inhibition of the malignant phenotype and restoration of homeostasis.
Key wordsGrowth factors Prostate cancer Gene therapy Hormone refractoriness
Fibroblast growth factor
Fibroblast growth factor receptor
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