Myc drives apoptosis in PC12 cells in the absence of Max

A conditionally active chimeric form of the c-Myc protein fused to the liga nd-binding domain of the estrogen receptor (MycER) was expressed in PC12 ce lls, Induction of Myc activity resulted in a threefold increase in apoptosi s after 5 days when cells were maintained in 1% serum, The effect of Myc ov erexpression was dependent on its DNA-binding domain but not on its heterod imeric binding protein Max, which is absent in PC12 cells, Preincubation of the c-Myc overexpressing cells with either NGF or bFGF, but not EGF, preve nted the Myc-mediated increase in apoptosis, although the signaling pathway s used by NGF and bFGF to block cell death differed, NGF-mediated rescue wa s mediated by the phosphatidylinositol 3 ' -OH (P13) kinase/Akt pathway whi te rescue by bFGF was not affected by P13 kinase inhibitors, These results show that Myc can induce apoptosis in PC12 cells in a Max-independent manne r and that alternate signaling pathways exist to mediate cell survival.