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

Lookup NU author(s): Dr Quentin Campbell Hewson, Professor Penny Lovat, Professor Andrew Pearson, Dr Chris Redfern

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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-β (RARβ) 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 RARβ mRNA by 9-cis or all-trans RA, or by LGD1069. RAR- and RXR-specific ligands used together induced CRABP-II and RARβ 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. © 2002 Wiley-Liss, Inc.


Publication metadata

Author(s): Campbell-Hewson, Q., Lovat, P.E., Pearson, A.D.J., Redfern, C.P.F.

Publication type: Article

Publication status: Published

Journal: Journal of Cellular Biochemistry

Year: 2002

Volume: 87

Issue: 3

Pages: 284-291

Print publication date: 01/01/2002

ISSN (print): 0730-2312

ISSN (electronic): 1097-4644

URL: http://dx.doi.org/10.1002/jcb.10310

DOI: 10.1002/jcb.10310

PubMed id: 12397610


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