Retinoid signalling and gene expression in neuroblastoma cells: RXR agonist and antagonist effects on CRABP-II and RARbeta expression.
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.
Hewson
Quentin Campbell
QC
Department of Child Health, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom.
Lovat
Penny E
PE
Pearson
Andrew D J
AD
Redfern
Christopher P F
CP
D000077556:Alitretinoin; D000077610:Bexarotene; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D047488:Retinoid X Receptors; D012176:Retinoids / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists* / Q000037:antagonists & inhibitors*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D013764:Tetrahydronaphthalenes; D014157:Transcription Factors; C082928:retinoic acid binding protein II, cellular; D000077556:Alitretinoin; D014212:Tretinoin; D000077610:Bexarotene