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Lovat, Penny E; Annicchiarico-Petruzzelli, Margherita; Corazzari, Marco; Dobson, Mark G; Malcolm, Archie J; Pearson, Andy D.J; Melino, Gerry; Redfern, Christopher P.F
FEBS letters, February 26, 1999, Letnik: 445, Številka: 2Journal Article
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.
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