Retinoid signalling and gene expression in neuroblastoma cells: RXR agonist and antagonist effects on CRABP-II and RARbeta expression.

Abstract

9-cis Retinoic acid (RA) induces gene expression in neuroblastoma cells more effectively and with different kinetics than other RA isomers, and could be acting in part through Retinoid X Receptors (RXRs). The aim of this study was to characterise the effects of an RXR agonist and RXR homodimer antagonist on the induction of cellular RA binding protein II (CRABP-II) and RA receptor-beta (RARbeta) in neuroblastoma cells in response to different retinoids. The RXR agonist, LDG1069, was as effective as all-trans RA in inducing gene expression, but less effective than 9-cis RA. The RXR-homodimer antagonist, LG100754, inhibited the induction of CRABP-II mRNA in SH-SY5Y neuroblastoma cells by 9-cis RA or the RXR-specific agonist LGD1069, but had no effect when used with all-trans RA. Conversely, LG100754 did not inhibit induction of RARbeta mRNA by 9-cis or all-trans RA, or by LGD1069. RAR- and RXR-specific ligands used together induced CRABP-II and RARbeta as effectively as 9-cis RA. These results demonstrate the value of combining RXR- and RAR-specific ligands to regulate RA-inducible gene expression. The possibility that RXR-homodimers mediate, in part, the induction of CRABP-II by 9-cis RA and RXR-specific ligands is discussed.

• Authors: Quentin Campbell Hewson, Penny E Lovat, Andrew D J Pearson, Christopher P F Redfern
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 87 Issue 3 Pg. 284-91 ( 2002) ISSN: 0730-2312 [Print] United States
• PMID: 12397610 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 Wiley-Liss, Inc.

Chemical References

• RNA, Messenger
• Receptors, Retinoic Acid
• Retinoid X Receptors
• Retinoids
• Tetrahydronaphthalenes
• Transcription Factors
• retinoic acid binding protein II, cellular
• Alitretinoin
• Tretinoin
• Bexarotene

Topics

• Alitretinoin
• Bexarotene
• Dose-Response Relationship, Drug
• Gene Expression (drug effects)
• Humans
• Neuroblastoma (metabolism)
• RNA, Messenger (biosynthesis)
• Receptors, Retinoic Acid (agonists, antagonists & inhibitors, biosynthesis, drug effects, genetics)
• Retinoid X Receptors
• Retinoids (chemistry, metabolism, pharmacology)
• Signal Transduction
• Tetrahydronaphthalenes (pharmacology)
• Transcription Factors (agonists, antagonists & inhibitors)
• Tretinoin (pharmacology)
• Tumor Cells, Cultured