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The Journal of Neuroscience, January 1, 2000, 20(1):230-239

The Urokinase Plasminogen Activator Receptor (UPAR) Is Preferentially Induced by Nerve Growth Factor in PC12 Pheochromocytoma Cells and Is Required for NGF-Driven Differentiation

Robin Farias-Eisner^{1, 2, 3}, Linda Vician^{2, 3, 4}, Abigail Silver³, Srinivasa Reddy⁵, Shafaat A. Rabbani⁶, and Harvey R. Herschman^{2, 3, 4}

Departments of ¹ Obstetrics and Gynecology, ² Biological Chemistry, ⁴ Molecular and Medical Pharmacology, and ⁵ Medicine and ³ Molecular Biology Institute, University of California, Los Angeles, Center for the Health Sciences, Los Angeles, California, and ⁶ Department of Medicine and Oncology, McGill University and Royal Victoria Hospital, Montreal, Quebec, Canada

Nerve growth factor (NGF)-driven differentiation of PC12 pheochromocytoma cells is a well studied model used both to identify molecular, biochemical, and physiological correlates of neurotrophin-driven neuronal differentiation and to determine the causal nature of specific events in this differentiation process. Although epidermal growth factor (EGF) elicits many of the same early biochemical and molecular changes in PC12 cells observed in response to NGF, EGF does not induce molecular or morphological differentiation of PC12 cells. The identification of genes whose expression is differentially regulated by NGF versus EGF in PC12 cells has, therefore, been considered a source of potential insight into the molecular specificity of neurotrophin-driven neuronal differentiation. A "second generation" representational difference analysis procedure now identifies the urokinase plasminogen activator receptor (UPAR) as a gene that is much more extensively induced by NGF than by EGF in PC12 cells. Both an antisense oligonucleotide for the UPAR mRNA and an antibody directed against UPAR protein block NGF-induced morphological and biochemical differentiation of PC12 cells; NGF-induced UPAR expression is required for subsequent NGF-driven differentiation.

Key words: urokinase plasminogen activator receptor; nerve growth factor; neurotrophin; PC12 pheochromocytoma cells; neuronal differentiation; primary response genes; immediate-early genes

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Copyright © 2000 Society for Neuroscience  0270-6474/0/201230-10$05.00/0

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