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

Publisher Website
Google Scholar
Abstract
Proto-oncogenes may be important in the cellular processes central for the growth and differentiation of normal cells1,2. 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 neuroblastoma4,26, 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 ganglioneuroma5,7,28. In vitro, many human neuroblastoma cell lines can be induced to differentiate morphologically and biochemically by a variety of agents6–11. 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 outgrowth8,9. 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.