7 pages, 4 figures.The β-amyloid protein, the major component of the vascular and plaque amyloid deposits that characterize Alzheimer's disease, derives from a larger β-amyloid precursor protein (APP) that is expressed in both neural and nonneural cells. An increased expression of APP might actively contribute to the development of the pathology; however, the mechanisms involved in the regulation of APP gene expression are not yet well understood. In PC12 cells, a rat pheochromocytoma cell line, we have demonstrated that nerve growth factor (NGF) induces the APP gene expression and increases APP mRNA levels in the presence of 0.5 or 15% serum. Expression of activated ras in the PC12 cell subline UR61 also leads to a significant increase in content of APP transcripts, and a dominant negative mutant of ras blocks the NGF-induced response. Other ligands of tyrosine kinase receptors, such as fibroblast growth factor, which causes morphological differentiation, or epidermal growth factor, which induces cell growth, also increase APP mRNA levels in PC12 cells. These results suggest that ras mediates the induction of APP gene expression by NGF and other ligands of tyrosine kinase receptors.M. J. Latasa is recipient of a fellowship\ud from the Departamento de Educación y Cultura del\ud Gobierno de Navarra. This work has been supported by\ud grants PB93-0135 from the DGICYT and FIS 94/0272.Peer reviewe