Distelhorst C W, Benutto B M, Griffith R C
Blood. 1985 Sep;66(3):679-85.
We determined the mol wt of glucocorticoid receptors in human leukemia cells in order to detect glucocorticoid receptor defects that might cause glucocorticoid resistance. Glucocorticoid receptors in intact cells were affinity labeled with [3H]dexamethasone-21-mesylate and were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Receptors in normal human peripheral blood mononuclear cells and six human leukemia cell lines had mol wt of 97,000. Malignant cells from ten of 25 patients with leukemia contained electrophoretically abnormal glucocorticoid receptors having mol wt of 55,000 in addition to normal size receptors (Mr = 97,000). The receptor abnormality was not restricted to a particular type of leukemia and was seen in cells from both newly diagnosed patients and patients who had received prior chemotherapy, including prednisone. The abnormal receptor was not generated when cells having only normal size receptors were assayed under conditions that favor proteolysis or when cytosol from cells containing the abnormal receptor form was mixed with cytosol from cells containing only normal size receptors. The mol wt of the abnormal receptors in human leukemia cells was the same as the mol wt of receptors in mutant mouse lymphoma cell lines, S49 143R and S49 55R, which have the nuclear transfer-increased phenotype of glucocorticoid resistance. This work describes for the first time a single common electrophoretic abnormality of glucocorticoid receptors in human leukemia cells. Further investigation of glucocorticoid receptor defects in human leukemia cells could lead to an improved understanding of the mechanisms of glucocorticoid resistance in leukemia as well as a method of predicting which patients are likely to be resistant to glucocorticoid therapy.
我们测定了人白血病细胞中糖皮质激素受体的分子量，以检测可能导致糖皮质激素抵抗的糖皮质激素受体缺陷。完整细胞中的糖皮质激素受体用[3H]甲磺酸地塞米松 - 21进行亲和标记，并通过十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳进行分析。正常人外周血单核细胞和六种人白血病细胞系中的受体分子量为97,000。25例白血病患者中有10例的恶性细胞除了正常大小的受体（Mr = 97,000）外，还含有电泳异常的糖皮质激素受体，其分子量为55,000。受体异常并不局限于某一特定类型的白血病，在新诊断患者以及接受过包括泼尼松在内的先前化疗的患者的细胞中均可见到。当仅具有正常大小受体的细胞在有利于蛋白水解的条件下进行检测时，或者当含有异常受体形式的细胞的胞质溶胶与仅含有正常大小受体的细胞的胞质溶胶混合时，不会产生异常受体。人白血病细胞中异常受体的分子量与突变小鼠淋巴瘤细胞系S49 143R和S49 55R中的受体分子量相同，这两种细胞系具有糖皮质激素抵抗的核转运增加表型。这项工作首次描述了人白血病细胞中糖皮质激素受体单一常见的电泳异常。对人白血病细胞中糖皮质激素受体缺陷的进一步研究可能会增进对白血病中糖皮质激素抵抗机制的理解，并提供一种预测哪些患者可能对糖皮质激素治疗耐药的方法。
