GROWTH-STIMULATION OF A431 CELLS BY EPIDERMAL GROWTH-FACTOR - IDENTIFICATION OF HIGH-AFFINITY RECEPTORS FOR EPIDERMAL GROWTH-FACTOR BY AN ANTI-RECEPTOR MONOCLONAL-ANTIBODY
GROWTH-STIMULATION OF A431 CELLS BY EPIDERMAL GROWTH-FACTOR - IDENTIFICATION OF HIGH-AFFINITY RECEPTORS FOR EPIDERMAL GROWTH-FACTOR BY AN ANTI-RECEPTOR MONOCLONAL-ANTIBODY
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DOI：
10.1073/pnas.80.5.1337
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发表时间：
1983-01-01
期刊：
影响因子：
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通讯作者：
MENDELSOHN, J
中科院分区：
文献类型：
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作者：
KAWAMOTO, T;SATO, JD;MENDELSOHN, J
表皮生长因子(EGF)在3 NM时最大限度地抑制[人]A431表皮样癌细胞的增殖。在较低浓度下，在3-100 PM范围内，EGF对A431细胞具有促有丝分裂作用。在100 nM的抗EGF受体单抗Ig G(528)存在下，抑制A431细胞的增殖并阻断95%的EGF结合，当EGF的浓度达到3 nM时，EGF对A431细胞有丝分裂作用。少数高亲和力的EGF受体可能参与刺激A431细胞的增殖。与~(125)I标记的EGF的饱和结合分析表明.apprxeq。0.1-0.2%的EGF受体是高亲和力受体，与EGF结合的Kd值估计为7倍。10-11M，这种亲和力比剩余的EGF受体高近两个数量级。尽管非饱和量的EGF(3 NM)最大限度地抑制了A431细胞的增殖，但528 Ig G(.apprxeq.70%的最大抑制率)需要饱和的抗体浓度(apprxeq.15海里)。与EGF不同的是，在528免疫球蛋白中没有观察到快速下调。结果提示，EGF和528免疫球蛋白抑制A431细胞生长的作用机制不同。
Epidermal growth factor (EGF) at 3 nM maximally inhibits the proliferation of [human] A431 epidermoid carcinoma cells. At lower concentrations, in the range of 3-100 pM, EGF has a mitogenic effect on A431 cells. In the presence of 100 nM anti-EGF-receptor monoclonal IgG (designated 528), which inhibits A431 cell proliferation and blocks > 95% of EGF binding, EGF becomes mitogenic for A431 cells at concentrations up to 3 nM. A minor population of high-affinity EGF receptors may be involved in stimulation of A431 cell proliferation. Saturation binding assays with 125I-labeled EGF indicate that .apprxeq. 0.1-0.2% of receptors for EGF are high-affinity receptors that bind EGF with an estimated Kd of 7 .times. 10-11 M. This affinity is nearly 2 orders of magnitude higher than that of the remaining EGF receptors. Although A431 cell proliferation is maximally inhibited by nonsaturating amounts of EGF (3 nM), maximal inhibition by 528 IgG(.apprxeq. 70% of maximal inhibition by EGF) requires saturating concentrations of antibody (.apprxeq. 15 nM). Unlike EGF, rapid down-regulation is not observed with 528 IgG. The results indicate different mechanisms of growth inhibition of A431 cells by EGF and 528 IgG.