Oncogenic Ras inhibits Fas ligand-mediated apoptosis by downregulating theexpression of Fas

Tumor growth is the result of deregulated tissue homeostasis which is maint ained through the delicate balance of cell growth and apoptosis, One of the most efficient inducers of apoptosis is the death receptor Fas, We report here that oncogenic Ras (H-Ras) downregulates Fas expression and renders ce lls of fibroblastic and epitheloid origin resistant to Fas ligand-induced a poptosis, In Ras-transformed cells, Fas mRNA is absent. Inhibition of DNA m ethylation restores Pas expression. H-Ras signals via the PI 3-kinase pathw ay to downregulate Fas, suggesting that the known anti-apoptotic effect of the downstream PKB/Akt kinase may be mediated, at least in part, by the rep ression of Fas expression. Thus, the oncogenic potential of H-ras may resid e on its capacity not only to promote cellular proliferation, but also to s imultaneously inhibit Fas-triggered apoptosis.