TRANSCRIPTIONAL REGULATION OF AMYLOID PRECURSOR PROTEIN DURING DIBUTYRYL CYCLIC AMP-INDUCED DIFFERENTIATION OF NG108-15 CELLS

Early expression of amyloid precursor protein (APP) during development of the nervous system suggests that this protein may play an importan t role first in axogenesis and later in synaptogenesis. To study regul ation of APP mRNA expression in neuronal cells, NG108-15 neuroblastoma x glioma cells were induced to differentiate in the presence of dibut yryl cyclic AMP. Steady-state levels of APP mRNA and APP isoforms incr eased gradually, concomitantly with the appearance of differentiated p henotype. Northern blot analysis showed a three-fold increase in APP e xpression at day 6 of dibutyryl cyclic AMP treatment. Nuclear run-on a ssays and transient transfections performed using APP promoter/reporte r constructs confirmed a twofold increase in the rate of APP gene tran scription. The stability of the mRNA was unchanged, with differentiate d and nondifferentiated cells having the same half-life of about 21 h. These results strongly suggest that APP mRNA induction in the differe ntiated NG108-15 cells is due to an increase in the rate of transcript ion of the gene.