DEXAMETHASONE MODULATES BINDING AND ACTION OF EPIDERMAL GROWTH-FACTOR IN SERUM-FREE CELL-CULTURE
DEXAMETHASONE MODULATES BINDING AND ACTION OF EPIDERMAL GROWTH-FACTOR IN SERUM-FREE CELL-CULTURE
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DOI：
10.1073/pnas.75.4.1882
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发表时间：
1978-01-01
影响因子：
11.1
通讯作者：
CUNNINGHAM, DD
中科院分区：
文献类型：
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作者：
BAKER, JB;BARSH, GS;CUNNINGHAM, DD
在人二倍体静息包皮细胞无血清培养上，探讨糖皮质激素调节细胞增殖的机制。单独添加合成糖皮质激素地塞米松对细胞数量无影响。然而，在所有EGF浓度下，地塞米松使HF细胞对表皮生长因子（EGF）的有丝分裂反应增强了50%。地塞米松浓度为100 ng/ml （0.25 .mu. m）时，EGF的促有丝分裂作用最大。与125i标记的EGF （125I-EGF）结合的研究表明，地塞米松通过调节EGF的细胞表面受体而引起这种“许可”效应。地塞米松处理的细胞在对EGF生长刺激的反应性增强的同时，其结合生理浓度的125I-EGF的能力也增加了50-100%。地塞米松治疗4小时后，结合明显增加。地塞米松处理的细胞在长时间暴露于刺激细胞分裂所需的EGF中保持了增加的结合125I-EGF的能力。此外，125I-EGF结合的增加表现出与增强EGF有丝分裂类似的地塞米松剂量依赖性，这表明地塞米松对结合和生长的影响之间存在关系。对结合增加的研究表明，它是糖皮质激素特异性的，需要蛋白质合成。125I-EGF结合的增强随着125I-EGF浓度的增加而减弱，这表明地塞米松引起了EGF受体的质变（可能是受体亲和力或协同性的改变）。125I-EGF结合的改变可能是地塞米松介导的细胞表面深远变化的一部分，因为地塞米松治疗轻微增加了HF细胞结合125i -胰岛素的能力，并使其结合125i -凝血酶的能力降低了一半。
Experiments probing the mechanism by which glucocorticoids modulate cell proliferation were carried out on serum-free cell cultures of quiescent human diploid foreskin (HF) cells. Added alone, the synthetic glucocorticoid dexamethasone had no effect on cell number. However, dexamethasone enhanced the mitogenic response of HF cells to epidermal growth factor (EGF) by 50% at all EGF concentrations. The mitogenic action of EGF was maximally promoted by a dexamethasone concentration of 100 ng/ml (0.25 .mu.M). Binding studies with 125I-labeled EGF (125I-EGF) suggested that dexamethasone caused this "permissive" effect by modulating cell surface receptors for EGF. Paralleling their increased responsiveness to EGF growth stimulation, dexamethasone-treated cells exhibited a 50-100% increased ability to bind physiological concentrations of 125I-EGF. A binding increase was apparent after a 4 h dexamethasone treatment. The dexamethasone-treated cells maintained an increased ability to bind 125I-EGF during the prolonged exposure to EGF that was required to stimulate cell division. Moreover, the increase in 125I-EGF binding exhibited a dexamethasone dose-dependence similar to that for the enhancement of EGF mitogenesis, suggesting a relationship between the dexamethasone effects on binding and growth. An investigation of the binding increase showed that it was specific for glucocorticoids, and required protein synthesis. The enhancement of 125I-EGF binding diminished with increasing concentrations of 125I-EGF, indicating that dexamethasone caused a qualitative change in the EGF receptors (possibly a change in receptor affinity or cooperativity). The alteration in 125I-EGF binding may occur as part of a far-reaching dexamethasone-mediated change in the cell surface, because dexamethasone treatment slightly increased the ability of HF cells to bind 125I-insulin, and decreased by half their ability to bind 125I-thrombin.