9-cis-Retinoic Acid Selectively Activates the Cellular Retinoic Acid Binding Protein-II Gene in Human Neuroblastoma Cells

Two families of nuclear retinoid receptors, retinoic acid receptor and retinoid X receptor (RAR and RXR respectively), and a family of cellular retinoic acid-binding proteins (CRABPI and II) participate in the retinoic acid (RA) signaling pathway. The presence and function of many of these receptors and cellular binding proteins have not been fully explored in RA-responsive human neuroblastoma cells. We have previously shown that RAR transcripts and protein are present in human neuroblastoma cells, and that all-trans RA induces the expression of the RARβ mRNA. In this paper, we demonstrate that human neuroblastoma cells express mRNA for RXR α and β. The mRNA for CRABPI is present in untreated human neuroblastoma cells, whereas the mRNA for CRABPII is induced in cells treated with either all-trans RA or 9-cis RA. Furthermore, 9-cis RA, a ligand that binds to both the RAR and the RXR families, selectively activates the CRABPII gene. In contrast, all-trans RA and 9-cis RA are equally effective in the induction of RARβ transcript and inhibition of cell proliferation. Since both retinoids inhibit human neuroblastoma cell proliferation, it appears that induction of RARβ rather than of CRABPII is more likely linked to the regulation of human neuroblastoma cell growth.