Receptor mechanisms mediating differentiation and proliferation effects ofretinoids on neuroblastoma cells

The aim of this study was to clarify retinoid receptor mechanisms mediating the effects of 9-cis retinoic acid (RA) and investigate the ability of RAR - and RXR-specific analogues to induce differentiation and inhibit prolifer ation in neuroblastoma cells. Differentiation and the inhibition of prolife ration by 9-cis RA, but not all-trans RA, were inhibited by the RXR-homodim er antagonist LG745. The RXR-specific agonist LGD1069 was ineffective at in ducing differentiation or inhibiting proliferation, but showed marked syner gism with RAR-specific agonists with respect to inhibiting proliferation. T hese data suggest that the effects of 9-cis RA are mediated via both RXR-ho modimers and heterodimers. However, combinations of RAR- and RXR-selective analogues were not as effective at promoting differentiation. This study in dicates that different receptor mechanisms are involved in retinoid-induced differentiation and inhibition of proliferation in neuroblastoma cells. (C ) 2000 Elsevier Science Ireland Ltd. All rights reserved.