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The Wistar Institute, Philadelphia Pennsylvania 19104
Farnesyltransferase inhibitors (FTIs) usually cause growth inhibition, but in certain preclinical settings they have been shown to induce apoptosis, a clinically desirable response. In this study, we show that the proapoptotic effects of FTIs in Ras-transformed cells are masked by activation of phosphatidylinositol 3'-kinase (PI3'K) or AKT, which are controlled by cytokines and integrins. The results implied that FTIs disrupt a signal that is crucial for survival of malignant cells, but not normal cells, if the PI3'K-AKT pathway is inactivated. Our findings have implications for clinical applications of FTIs where apoptotic responses would be preferred.
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