Identification of genes preferentially induced by nerve growth factor versus epidermal growth factor in PC12 pheochromocytoma cells by means of representational difference analysis.

Neurotrophins induce neuronal differentiation by binding to a subclass of ligand-stimulated protein tyrosine kinase receptors and activating signal transduction pathways that mediate altered patterns of gene expression. Nerve growth factor (NGF) induced differentiation of PC12 pheochromocytoma cells is one of the major model systems used to study neuronal differentiation in response to neurotrophins. Although epidermal growth factor (EGF) does not induce PC12 cell differentiation, NGF and EGF activate many of the same signal transduction pathways and induce transcription of many of the same genes in PC12 cells. We have now employed cDNA representational difference analysis to identify four genes (activity-regulated cytoskeletal protein, collagenase 1, plasminogen activator inhibitor-1, and VH6/MKP-3) as genes preferentially induced withing 4 hours by NGF in PC12 cells.