Premium
Differential effects of retinoic acid isomers on the expression of nuclear receptor co‐regulators in neuroblastoma
Author(s) -
Lovat Penny E,
Annicchiarico-Petruzzelli Margherita,
Corazzari Marco,
Dobson Mark G,
Malcolm Archie J,
Pearson Andy D.J,
Melino Gerry,
Redfern Christopher P.F
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00162-3
Subject(s) - retinoic acid receptor gamma , retinoic acid , retinoic acid inducible orphan g protein coupled receptor , neuroblastoma , chemistry , retinoic acid receptor , nuclear receptor , retinoic acid receptor beta , receptor , retinoic acid receptor alpha , retinoid x receptor gamma , differential (mechanical device) , microbiology and biotechnology , cancer research , biology , biochemistry , transcription factor , genetics , gene , cell culture , physics , thermodynamics
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.