Transcriptional regulation of amyloid precursor protein during dibutyryl cyclic AMP-induced differentiation of NG108-15 cells

Abstract

Early expression of amyloid precursor protein (APP) during development of the nervous system suggests that this protein may play an important role first in axogenesis and later in synaptogenesis. To study regulation of APP mRNA expression in neuronal cells, NG108-15 neuroblastoma x glioma cells were induced to differentiate in the presence of dibutyryl cyclic AMP. Steady- state levels of APP mRNA and APP isoforms increased gradually, concomitantly with the appearance of differentiated phenotype. Northern blot analysis showed a threefold increase in APP expression at day 6 of dibutyryl cyclic AMP treatment. Nuclear run-on assays and transient transfections performed using APP promoter/reporter constructs confirmed a twofold increase in the rate of APP gene transcription. The stability of the mRNA was unchanged, with differentiated and nondifferentiated cells having the same half-life of about 21 h. These results strongly suggest that APP mRNA induction in the differentiated NG108-15 cells is due to an increase in the rate of transcription of the gene.