FIG. 1.

p53 tumor suppression in brain epithelium. The diagram depicts previously elucidated steps in the development of choroid plexus tumors in TgT₁₂₁ mice. (A) Cell-specific expression of the T₁₂₁ transgene induces proliferation of normally nondividing epithelial cells by inactivating the pRb family proteins pRb, p107, and p130. p53-dependent apoptosis is then activated, as evidenced by the 85% reduction in apoptosis in TgT₁₂₁;p53^−/− mice. (B) Using a genetic approach, we previously showed that E2F1 acts upstream of p53 to induce apoptosis in response to T₁₂₁. Previously, E2F1 was shown to activate p19^ARF transcription, and p19^ARF was shown to induce p53 activities by regulating Mdm2 in cultured cells (see the introduction). In the current report, we tested whether this pathway is operative to induce p53-dependent apoptosis and suppression of brain epithelial tumors in vivo.