The urokinase plasminogen activator receptor (UPAR) is preferentially induced by nerve growth factor in PC12 pheochromocytoma cells and is required for NGF-driven differentiation

Nerve growth factor (NGF)-driven differentiation of PC12 pheochromocytoma c ells is a well studied model used both to identify molecular, biochemical, and physiological correlates of neurotrophin-driven neuronal differentiatio n and to determine the causal nature of specific events in this differentia tion process. Although epidermal growth factor (EGF) elicits many of the sa me early biochemical and molecular changes in PC12 cells observed in respon se to NGF, EGF does not induce molecular or morphological differentiation o f PC12 cells. The identification of genes whose expression is differentiall y regulated by NGF versus EGF in PC12 cells has, therefore, been considered a source of potential insight into the molecular specificity of neurotroph in-driven neuronal differentiation. A "second generation" representational difference analysis procedure now identifies the urokinase plasminogen acti vator receptor (UPAR) as a gene that is much more extensively induced by NG F than by EGF in PC12 cells. Both an antisense oligonucleotide for the UPAR mRNA and an antibody directed against UPAR protein block NGF-induced morph ological and biochemical differentiation of PC12 cells; NGF-induced UPAR ex pression is required for subsequent NGF-driven differentiation.