Differential effects of 9-cis, 13-cis and all-trans retinoic acids on the neuronal differentiation of human neuroblastoma cells.
A human neuroblastoma cell line IMR-32 was used as an in vitro model to examine three naturally occurring retinoic acid (RA) isomers, 9-cis (9c), 13-cis (13c) and all-trans (AT) RA, in mediating growth differentiation and neuronal differentiation. All RA isomers inhibited cellular proliferation, with 13c-RA being most effective. Cyclic AMP-responsive-element-binding-protein (CREB) was activated during RA treatment. AT-RA was a better differentiating agent in inducing the highest expression of the neurotrophic factor receptor TrkA. After prolonged RA treatment, the expression of RA receptors (RARs) was comparable for the three isomers, but retinoid X receptors (RXRs) were differentially regulated. These results imply that distinctive molecular pathways might be involved in the in vitro differentiation of neuroblastoma with different RA isomers.
Chu
Patrick W K
PW
University Department of Medicine, Queen Mary Hospital, Hong Kong.
Cheung
William M W
WM
Kwong
Yok L
YL
D015415:Biomarkers; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology*; D009474:Neurons / Q000187:drug effects*; D020917:Receptor, trkA / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000378:metabolism; D047488:Retinoid X Receptors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013237:Stereoisomerism; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism; D014162:Transfection; D014212:Tretinoin / Q000737:chemistry / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000378:metabolism
D015415:Biomarkers; D017362:Cyclic AMP Response Element-Binding Protein; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin; D020917:Receptor, trkA; D001616:beta-Galactosidase