Retinoic acid up-regulates nuclear retinoic acid receptor-α expression in human neuroblastoma cells

✍ Scribed by Laura Wuarin; Bieshia Chang; Randal Wada; Neil Sidell

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: French
• Weight: 973 KB
• Volume: 56
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910560615

✦ Synopsis

Publication of the International Union Against Cancer Publication de I Union Internationale Contre le Cancer Retinoic acid (RA) nuclear receptors (RARs) are thought to mediate the cellular and molecular effects of RA on a wide variety of tissues. In most cell types, RARa expression remains relatively constant following exposure to RA, while that of RARP is rapidly induced. In this study, we show that in human neuroblastoma, a cell type exceptionally sensitive to RAinduced differentiation, RARa as well as RARP is markedly up-regulated by RA treatment. This effect was consistent in all 5 neuroblastoma cell lines tested and was reflected in a 2to 5-fold increase in receptor mRNA levels as assessed by Northernblot analysis. Using LA-N-5 human neuroblastoma cells, we found that receptor up-regulation occurred in a time-and dose-dependent fashion with increases in both RARa and P mRNA detectable 1-2 hr after the addition of RA. These inductions were not abrogated by cycloheximide, indicating that protein synthesis was not required for the RA responses. Nuclear run-off experiments combined with Northern-blot analysis of RARa stability directly demonstrated that the upregulation of RARa mRNA levels reflected an increased rate of transcription without changes in message half-life. These findings, showing direct activation by RA of RARa gene transcription in human neuroblastoma cells, suggest differences in the overall regulation of this receptor from that found in most other RA-inducible tissue.