RETINOIDS AND A RETINOIC ACID RECEPTOR DIFFERENTIALLY MODULATE THYMOSIN-BETA-10 GENE-EXPRESSION IN TRANSFECTED NEUROBLASTOMA-CELLS

1. Investigations have demonstrated that the gene encoding thymosin beta-10 (a 43-amino acid member of a family of related proteins originally described in the rat immune system) is a target for morphogenic retinoids in both human and rat neuroblastoma cells. 2. Structure-activity studies revealed that the stimulatory actions of retinoids upon the thymosin beta-10 gene reflect the differing affinities of retinoid analogues for a retinoic acid receptor. 3. To examine further the possibility that the trophic actions of retinoic acid upon expression of the thymosin beta-10 gene involved retinoid receptors, neuroblastoma cells were transiently transfected with an expression vector encoding the nuclear retinoic acid receptor (alpha) protein. 4. Northern blot and slot-blot analyses revealed that neuronal cells overexpressing RAR-alpha-mRNA exhibited an enhanced sensitivity to exogenous and endogeneous retinoic acid in terms of thymosin beta-10 mRNA. Although the RAR-alpha gene was expressed (at low levels) a priori in these neuroblastoma cells, retinoic acid (2 x 10(-7) M for 3 days) slightly stimulated RAR-alpha-mRNA accumulation. 5. Collectively, these findings indicate the the retinoic acid receptor (alpha) is regulated by retinoid acid and that the developmentally regulated, retinoid-responsive thymosin beta-10 gene is a target for this nuclear transcription factor in cells derived from the neural crest.