The function of amyloid precursor protein (APP) was investigated in human neuroblastoma La-N-1 cells by stable transfection with a DNA construct encoding antisense APP mRNA. Levels of APP mRNA, as well as proteins, were reduced by 80-90% in antisense APP transfected (ASAT) cells. ASAT cells exhibited three main features as a result of APP gene expression deprivation: (1) a 30% reduction in cell proliferation, (2) reduced cell adhesion that could be reversed by the addition of La-N-1 conditioned media as a source of secreted APP, and (3) a two- and four-fold increase in neurite-bearing cells suggesting that cellular APP may be involved in neurite extension. The first two features confirm previously reported functions for APP in proliferation and adhesion of non-neuronal cell types but the use of neuroblastoma cells in this study disclose a novel role for cellular APP in neurite extension.