EXPRESSION AND RETINOID MODULATION OF N-ARGININE DIBASIC CONVERTASE AND AN AMINOPEPTIDASE-B IN HUMAN NEUROBLASTOMA CELL-LINES

Under retinoic acid exposure, the three SK-N-BE(2)-derived human neuro blastoma cell lines, BE(2)-NA, BE(2)-SA and BE(2)-M17 undergo mainly d ifferentiation, apoptosis or continue to proliferate, respectively. We have used this model system to study the modulation of the transcript ional expression of putative processing enzymes, two novel metallopept idases; i.e. N-arginine dibasic convertase (NRD convertase; EC 3.4.24. 61) and an aminopeptidase-B after exposure of the cells either to reti noic acid or to synthetic retinoid analogs. The data indicate that the two respective enzymes are differently modulated in the various cell lines. Whereas aminopeptidase-B expression is enhanced in most cases, NRD convertase appears to undergo opposite regulation in proliferating versus differentiating neuroblastoma cells. It is concluded that both genes might contain retinoic acid regulatory elements (RARE) in their promoters.