Differential effects of retinoic acid isomers on the expression of nuclear receptor co-regulators in neuroblastoma.
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 TIF1alpha, TIF1beta, 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 TIF1alpha, TIF1beta 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.
Lovat
P E
PE
Department of Child Health, Medical School, University of Newcastle, Newcastle Upon Tyne, UK.
Annicchiarico-Petruzzelli
M
M
Corazzari
M
M
Dobson
M G
MG
Malcolm
A J
AJ
Pearson
A D
AD
Melino
G
G
Redfern
C P
CP
D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007536:Isomerism; D060588:LIM Domain Proteins; D009447:Neuroblastoma; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D056985:Nuclear Receptor Co-Repressor 2; D046988:Proteasome Endopeptidase Complex; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics*; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D000076183:Tripartite Motif-Containing Protein 28; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C539130:NCOR2 protein, human; D009687:Nuclear Proteins; D056985:Nuclear Receptor Co-Repressor 2; C092282:PSMC5 protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D047488:Retinoid X Receptors; C106843:SUG1 protein, mammalian; D014157:Transcription Factors; C093517:transcriptional intermediary factor 1; D014212:Tretinoin; C101116:TRIM28 protein, human; D000076183:Tripartite Motif-Containing Protein 28; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities