Receptor mechanisms mediating differentiation and proliferation effects of retinoids on neuroblastoma cells.
The aim of this study was to clarify retinoid receptor mechanisms mediating the effects of 9-cis retinoic acid (RA) and investigate the ability of RAR- and RXR-specific analogues to induce differentiation and inhibit proliferation in neuroblastoma cells. Differentiation and the inhibition of proliferation by 9-cis RA, but not all-trans RA, were inhibited by the RXR-homodimer antagonist LG745. The RXR-specific agonist LGD1069 was ineffective at inducing differentiation or inhibiting proliferation, but showed marked synergism with RAR-specific agonists with respect to inhibiting proliferation. These data suggest that the effects of 9-cis RA are mediated via both RXR-homodimers and heterodimers. However, combinations of RAR- and RXR-selective analogues were not as effective at promoting differentiation. This study indicates that different receptor mechanisms are involved in retinoid-induced differentiation and inhibition of proliferation in neuroblastoma cells.
Hewson
Q C
QC
Department of Child Health, University of Newcastle upon Tyne, UK.
Lova
P E
PE
Malcolm
A J
AJ
Pearson
A D
AD
Redfern
C P
CP
D000077556:Alitretinoin; D000077610:Bexarotene; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D019281:Dimerization; D006801:Humans; D009447:Neuroblastoma; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D047488:Retinoid X Receptors; D012176:Retinoids / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D013764:Tetrahydronaphthalenes; D014157:Transcription Factors; D000077556:Alitretinoin; D014212:Tretinoin; D000077610:Bexarotene