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Receptor mechanisms mediating differentiation and proliferation effects of retinoids on neuroblastoma cells

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

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Abstract

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. Copyright (C) 2000 Elsevier Science Ireland Ltd.


Publication metadata

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

Publication type: Article

Publication status: Published

Journal: Neuroscience Letters

Year: 2000

Volume: 279

Issue: 2

Pages: 113-116

Print publication date: 28/01/2000

ISSN (print): 0304-3940

ISSN (electronic): 1872-7972

URL: http://dx.doi.org/10.1016/S0304-3940(99)00956-8

DOI: 10.1016/S0304-3940(99)00956-8

PubMed id: 10674634


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