Differential effects of retinoic acid isomers on the expression of nuclear receptor co‐regulators in neuroblastoma

FEBS Letters

Dobson, Mark G¹  Lovat, Penny E²  Redfern, Christopher P.F¹  Pearson, Andy D.J²  Melino, Gerry³  Corazzari, Marco³  Annicchiarico-Petruzzelli, Margherita³  Malcolm, Archie J⁴ 

[1] Department of Medicine, Medical School, University of Newcastle, Newcastle Upon Tyne NE2 4HH, UK;Department of Child Health, Medical School, University of Newcastle, Newcastle Upon Tyne NE2 4HH, UK;IDI-IRCCS laboratory, Department of Experimental Medicine, University of Rome, Tor Vergata, Rome 00133, Italy;Department of Pathology, Medical School, University of Newcastle, Newcastle Upon Tyne NE2 4HH, UK

关键词: Neuroblastoma;    Co-activator;    Co-repressor;    All-trans retinoic acid;    9-cis retinoic acid;    SMRT;    Trip3;    TIF1;   

DOI  :  10.1016/S0014-5793(99)00162-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Retinoic acid modulates growth and induces differentiation and apoptosis of neuroblastoma cells in vitro, with the all-trans and 9-cis isomers having different biological properties. Transcriptional activation in response to retinoic acid isomers is mediated by retinoic acid receptors and retinoid X receptors. The differential expression of co-activators and co-repressors which preferentially interact with retinoic acid receptors or retinoid X receptors may be a mechanism leading to different cellular responses to 9-cis and all-trans retinoic acid. To test this hypothesis, we have studied the expression of the nuclear receptor co-regulators TIF1α, TIF1β, SUG1 and SMRT in the N-type and S-type neuroblastoma cell lines SH SY 5Y and SH S EP. Transcripts for all four co-regulators were expressed in these neuroblastoma cells. The expression of TIF1α, TIF1β and SUG1 did not change in response to retinoic acid; however, SMRT was induced in both neuroblastoma cell lines, but particularly by all-trans retinoic acid in SH S EP cells. An additional co-activator, Trip3, was isolated by differential mRNA display and shown to be preferentially induced by 9-cis retinoic acid in SH SY 5Y and SH S EP cells. These data suggest that retinoic acid isomer-specific induction of nuclear receptor co-regulators may determine, in part, the differential biological effects of retinoic acid isomers.

【 授权许可】

Unknown