MODULATION OF PROTEIN KINASE ACTIVITY BY GENISTEIN IN PROSTATE CANCER

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Genistein is an isoflavinoid which is found in high amounts in soy. Its consumption has been associated with a low incidence of prostate cancer (PCa). This project sought to elucidate potential mechanisms by which genistein may have potential therapeutic effects upon prostate cancer. Our studies elucidated a potential antimetastatic effect by demonstrating that genistein increased the adhesion of PCa cells to solid matrix. Increased adhesion was shown to be time and concentration dependent, with adhesion related effects evident at genistein concentrations as low as 1 nM (with dietary consumption, average serum concentrations of free genistein are 10 nM). Associated with changes in cell morphology was the translocation of focal adhesion kinase (FAK; a tyrosine kinase) from the cytoplasm to membrane associated focal adhesion plaques (focal areas of cell adhesion to extracellular solid matrix). At the membrane, FAK formed a complex with beta-1-integrin (an important transmembrane cell adhesion molecule). The activity of FAK autokinase activity transiently increased during the process of cell adhesion, thereafter it decreased to below baseline levels.