Differential gene regulation by 9-cis and all-trans retinoic acid in neuroblastoma cells.
BACKGROUND
9-cis retinoic acid (RA) is more effective than all-trans RA at inducing neuroblastoma differentiation in vitro, and has distinct biological properties with respect to its ability to promote apoptosis in N-type neuroblastoma cells. The cellular effects of 9-cis RA may, in part, result from activation of retinoid X receptor (RXR) homodimers. If this hypothesis is correct, 9-cis RA may control the expression of a different subset of retinoid-regulated genes compared to all-trans RA.


METHODS
We have therefore used differential mRNA display to identify genes differentially expressed in neuroblastoma cells in response to all-trans and 9-cis RA.


RESULTS
The majority of cDNAs differentially expressed in response to all-trans or 9-cis RA matched to nonredundant Genbank sequences or EST database sequences. Differential-display profiles were similar in SH SY 5Y and SH S EP cells, clonal derivatives of the mixed neuroblastoma cell line SK N SH, although there were apparent differences between these cell lines with respect to the retinoid-regulation of specific RT-PCR cDNA fragments.


CONCLUSIONS
These data support the view that 9-cis and all-trans RA act via different receptor mechanisms.
Lovat
P E
PE
Department of Medicine, Medical School, University of Newcastle Upon Tyne, United Kingdom.
Dobson
M
M
Malcolm
A J
AJ
Pearson
A D
AD
Redfern
C P
CP
D000077556:Alitretinoin; D017209:Apoptosis / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018076:DNA, Complementary; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018168:Receptors, Retinoic Acid; D000077556:Alitretinoin; D014212:Tretinoin