RETINOIC ACID RECEPTOR-BETA AND RECEPTOR-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 hav e transfected a human neuroblastoma tumor cell line with a vector expr essing 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 tr ansfectant clones overexpressing RARs alpha and gamma had no significa nt reduction in cell growth rates. Although RAR gamma transfectants we re sensitive to the growth inhibitory effects of exogenous retinoids, these cells demonstrated resistance to the neuritogenic retinoid effec ts. Only RAR beta transfectants exhibited increased sensitivity to ret inoids added in vitro. These results suggest that distinct neuritogeni c and growth inhibitory signalling pathways exist in neuroblastoma cel ls and that RAR beta expression may be necessary for the retinoid grow th inhibitory pathway. (C) 1996 Academic Press, Inc.