Cheung B, Hocker J E, Smith S A, Reichert U, Norris M D, Haber M, Stewart B W, Marshall G M
Children's Cancer Research Institute, Sydney Children's Hospital, Randwick, Australia.
Biochem Biophys Res Commun. 1996 Dec 4;229(1):349-54. doi: 10.1006/bbrc.1996.1804.
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.
维甲酸可诱导人神经母细胞瘤细胞显著的生长抑制和神经突分化。胚胎组织和成年组织中核视黄酸受体（RAR）的表达模式表明，RAR亚型α、β和γ具有组织特异性功能。我们用表达人RARα、β或γ cDNA的载体转染了一种人神经母细胞瘤肿瘤细胞系。在没有外源性维甲酸的情况下，RARβ转染细胞表现出显著的生长抑制，但无分化的形态学证据，而过度表达RARα和γ的转染克隆细胞生长速率无显著降低。尽管RARγ转染细胞对外源性维甲酸的生长抑制作用敏感，但这些细胞对维甲酸诱导神经突生长的作用具有抗性。只有RARβ转染细胞对体外添加的维甲酸表现出更高的敏感性。这些结果表明，神经母细胞瘤细胞中存在不同的神经突生长诱导和生长抑制信号通路，并且RARβ的表达可能是维甲酸生长抑制通路所必需的。
