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人髓性白血病细胞系中糖皮质激素敏感性与受体

Glucocorticoid sensitivity and receptors in cells of human myelogenous leukemia lines.

作者信息

Koeffler H P, Golde D W, Lippman M E

出版信息

Cancer Res. 1980 Mar;40(3):563-6.

PMID:6937238
Abstract

The effect of dexamethasone on the clonal proliferation of human acute myelogenous leukemia cells was studied using the two available human acute myelogenous leukemia lines KG-1 and HL-60. The cells were cloned in agar in the presence of colony-stimulating activity with and without dexamethasone. Colony formation by KG-1 cells was inhibited by dexamethasone at a concentration of 10(-7) M, and a 50% reduction occurred at 10(-5) M dexamethasone. Dexamethasone had no effect on HL-60 colony formation. Direct assessment of dexamethasone binding showed that both KG-1 and HL-60 cells had high-affinity glucocorticoid receptors with a mean 10,300 and 15,600 binding sites/cell with a Kd of 3.3 x 10(-9) M and 4.2 x 10(-9) M (r greater than or equal to -0.95), respectively. Binding competition studies confirmed the specificity of these glucocorticoid receptors. No correlation was noted between the number of glucocorticoid receptors and the in vitro inhibition of colony formation. A variety of other steroids was tested and found to have no effect on clonal proliferation of the leukemic cells.

摘要

利用现有的两种人类急性髓性白血病细胞系KG - 1和HL - 60,研究了地塞米松对人类急性髓性白血病细胞克隆增殖的影响。细胞在有或无地塞米松存在的情况下,于含有集落刺激活性的条件下在琼脂中进行克隆。地塞米松在浓度为10(-7) M时抑制KG - 1细胞的集落形成,在10(-5) M地塞米松时集落形成减少50%。地塞米松对HL - 60细胞的集落形成无影响。地塞米松结合的直接评估显示,KG - 1和HL - 60细胞均具有高亲和力的糖皮质激素受体,平均每个细胞分别有10300和15600个结合位点,解离常数分别为3.3×10(-9) M和4.2×10(-9) M(r≥ - 0.95)。结合竞争研究证实了这些糖皮质激素受体的特异性。未发现糖皮质激素受体数量与体外集落形成抑制之间存在相关性。测试了多种其他类固醇,发现它们对白血病细胞的克隆增殖无影响。

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