TY - JOUR T1 - FGF Induces a Switch in Death Receptor Pathways in Neuronal Cells JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4996 LP - 5006 DO - 10.1523/JNEUROSCI.21-14-04996.2001 VL - 21 IS - 14 AU - Eva M. Eves AU - Christine Skoczylas AU - Keiko Yoshida AU - Emad S. Alnemri AU - Marsha R. Rosner Y1 - 2001/07/15 UR - http://www.jneurosci.org/content/21/14/4996.abstract N2 - Basic fibroblast growth factor (FGF2) has many roles in neuronal development and maintenance including effects on mitogenesis, survival, fate determination, differentiation, and migration. Using a conditionally immortalized rat hippocampal cell line, H19-7, and primary hippocampal cultures, we now demonstrate that FGF2 treatment differentially regulates members of the tumor necrosis factor (TNF) superfamily of death domain receptors and their ligands. H19-7 cells transferred from serum to defined (N2) medium undergo apoptosis by a Fas-dependent mechanism similar to primary neurons. In contrast, H19-7 cells treated with FGF undergo apoptosis by a Fas-independent mechanism. FGF suppresses the Fas death pathway but also induces apoptosis by activation of a TNFα death pathway in both H19-7 and hippocampal progenitor cells. Expression of the TNF receptor 1 (TNFR1) or TNFR2 in H19-7 cells is sufficient to sensitize the cells to TNFα, similar to the effects of FGF. Because TNFα can be either proapoptotic or antiapoptotic, these results provide an explanation for the divergent trophic effects of FGF2 treatment and the observation that multiple trophic inputs are required for the survival of specific neurons. ER -