Norman M R, Thompson E B
Cancer Res. 1977 Oct;37(10):3785-91.
A human lymphoblastoid cell line (CEM), the growth of which is inhibited by glucocorticoids, is described. Although growth of the original uncloned cell line is only slightly retarded by dexamethasone, sensitive clones were isolated in which growth is completely blocked by 2 to 3 days of exposure to 10(-6) M dexamethasone. After 4 to 5 days, these cells become pyknotic and lyse. The inhibitory affect of dexamethasone first become apparent in suspension culture at a concentration of about 5 X 10(-8) M. Receptor analysis showed the presence of specific glucocorticoid receptors with an apparent dissociation constant for dexamethasone of about 1.3 X 10(-8) M both in the sensitive and in one resistant clone analyzed. Ability to displace dexamethasone from the receptor is correlated with the known glucocorticoid activity of all steroids tested, as is their ability to inhibit cloning of sensitive cells in agarose. These results indicate that the specificity of inhibitory effects is related to receptor specificity of inhibitory effects is related to receptor specificity. Dexamethasone is a potent inhibitor when cells are cloned in agarose, having a marked effect even at a concentration of 7 X 10(-9) M. CEM cells thus provide human cell lines suitable for in vitro analysis of steroid effects on leukemic cells.
本文描述了一种人淋巴母细胞系(CEM),其生长受糖皮质激素抑制。虽然原始未克隆细胞系的生长仅被地塞米松轻微抑制,但分离出了敏感克隆,在这些克隆中,暴露于10^(-6) M地塞米松2至3天可完全阻断生长。4至5天后,这些细胞会发生核固缩并裂解。地塞米松的抑制作用在悬浮培养中约5×10^(-8) M的浓度下首次显现。受体分析表明,在所分析的敏感克隆和一个抗性克隆中均存在特异性糖皮质激素受体,其对地塞米松的表观解离常数约为1.3×10^(-8) M。从受体上取代地塞米松的能力与所有测试类固醇已知的糖皮质激素活性相关,它们在琼脂糖中抑制敏感细胞克隆的能力也与之相关。这些结果表明,抑制作用的特异性与受体特异性有关。当地塞米松用于琼脂糖中的细胞克隆时是一种强效抑制剂,即使在7×10^(-9) M的浓度下也有显著作用。因此,CEM细胞提供了适合体外分析类固醇对白血病细胞作用的人细胞系。