Retinoic acid receptors beta and gamma distinguish retinoid signals for growth inhibition and neuritogenesis in human neuroblastoma cells.
Retinoids induce marked growth inhibition and neuritic differentiation in human neuroblastoma cells. Expression patterns of nuclear retinoic acid receptors (RAR) in embryonic and adult tissues suggests that RAR subtypes alpha, beta and gamma have tissue-specific functions. We have transfected a human neuroblastoma tumor cell line with a vector expressing either human RAR alpha, beta or gamma cDNAs. In the absence of exogenous retinoid, RAR beta transfectants demonstrated marked growth inhibition without morphologic evidence of differentiation, whereas transfectant clones overexpressing RARs alpha and gamma had no significant reduction in cell growth rates. Although RAR gamma transfectants were sensitive to the growth inhibitory effects of exogenous retinoids, these cells demonstrated resistance to the neuritogenic retinoid effects. Only RAR beta transfectants exhibited increased sensitivity to retinoids added in vitro. These results suggest that distinct neuritogenic and growth inhibitory signalling pathways exist in neuroblastoma cells and that RAR beta expression may be necessary for the retinoid growth inhibitory pathway.
Cheung
B
B
Children's Cancer Research Institute, Sydney Children's Hospital, Randwick, Australia.
Hocker
J E
JE
Smith
S A
SA
Reichert
U
U
Norris
M D
MD
Haber
M
M
Stewart
B W
BW
Marshall
G M
GM
D002454:Cell Differentiation; D002455:Cell Division; D006801:Humans; D016501:Neurites / Q000502:physiology*; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology*; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D000097768:Retinoic Acid Receptor gamma
D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D012176:Retinoids; D000097768:Retinoic Acid Receptor gamma; C082925:retinoic acid receptor beta