Differential expression of N-myc and c-src proto-oncogenes during neuronal and schwannian differentiation of human neuroblastoma cells.

Neuroblastoma (NB) cells can be induced to differentiate bidirectionally into either neuronal or schwannian cells by different inducers. However, the underlying mechanisms are poorly understood. We examined the expression of N-myc and c-src genes in 3 human NB-cell lines during either neuronal or schwannian differentiation in vitro, since proto-oncogenes are considered to play a pivotal role in regulating cell proliferation and differentiation. Decreased N-myc expression and increased c-src expression were observed during neuronal differentiation by retinoic acid, polyprenoic acid (E5166) and dibutyryl cyclic AMP, whereas the expression of N-myc and c-src genes was considerably reduced during schwannian differentiation by bromodeoxyuridine, demonstrating that the expression of N-myc and c-src genes was regulated independently in the bipolar differentiation processes of NB cells. Our results suggest that enhanced N-myc expression might be closely linked to the undifferentiated phenotypes of NB cells, that c-src expression might be related to the neuronal differentiation of NB cells, and that N-myc and c-src genes might be regulated independently in the determination of the bipolar differentiation of NB cells.