Regulation of retinoic acid receptor alpha expression in human neuroblastoma cell lines and tumor tissue.
Human neuroblastoma (NB) cell lines treated with all-trans retinoic acid (RA) differentiate in culture, forming neurites and exhibiting growth arrest. We treated 5 human NB cell lines with RA, and observed a 2-5 fold induction of retinoic acid receptor alpha (RAR alpha) mRNA expression in 4 of the 5 cell lines, as an early cellular response. Induction of RAR alpha expression was specific for RA among several differentiating agents tested. RAR alpha mRNA expression in 13 primary neuroblastoma tumor samples was 3 fold higher in localised compared with advanced tumors (p < 0.05). RAR alpha expression may be necessary for the effects of RA on NB cells in vitro and reduced expression of this gene in vivo may contribute to the process of NB tumorigenesis.
Children's Leukaemia and Cancer Research Centre, Prince of Wales Children's Hospital, Randwick, Sydney, Australia.
G M
GM
Marshall
B
B
Cheung
K P
KP
Stacey
M D
MD
Norris
M
M
Haber
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D015342:DNA Probes; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis*; D000072482:Retinoic Acid Receptor alpha; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015342:DNA Probes; C000607071:RARA protein, human; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate