Decreased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma

Abstract

Proto-oncogenes may be important in the cellular processes central for the growth and differentiation of normal cells^1,2. N-myc is a DNA sequence which shares limited homology to the protooncogene c-myc and has been found to be amplified in both primary tissue³ and cell lines from neuroblastoma^4,26, a childhood tumour of neuroectodermal origin. Differentiation of this embryonal tumour is of clinical importance, since occasional tumours have been noted to differentiate in vivo to benign ganglioneuroma^5,7,28. In vitro, many human neuroblastoma cell lines can be induced to differentiate morphologically and biochemically by a variety of agents^6–11. Retinoic acid (RA), an analogue of vitamin A, has been shown to inhibit neuroblastoma cell growth and clonability in soft agar, and to induce extensive neurite outgrowth^8,9. Therefore we examined the relationship of N-myc expression to the in vitro differentiation of these cells. We report here that in the case of RA-induced differentiation, a decreased level of expression is detected within 6 h of treatment and precedes both cell-cycle changes and morphological differentiation.