Retinoids specifically enhance the number of epidermal growth factor receptors

Retinoids specifically enhance the number of epidermal growth factor receptors
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DOI:
10.1038/284626a0
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发表时间:
1980-04
期刊:
影响因子:
64.8
通讯作者:
A. Jetten
A. Jetten
中科院分区:
综合性期刊1区
文献类型:
--
作者:
A. Jetten

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维甲酸在体外引起细胞的许多生物学和生化反应1 -5。细胞对类维生素A的反应性的一个广泛使用的标准是生长抑制;类维生素A降低许多正常和致瘤细胞系的饱和密度和/或生长速率2,6,7。已经证明真核细胞的增殖依赖于大分子生长因子如表皮生长因子(EGF)8-10的存在,其可以刺激上皮和成纤维细胞系的增殖。我们现在描述类维生素A对EGF与其受体结合的影响。视黄酸增强125 I标记的EGF与各种成纤维细胞和表皮细胞系的结合。它对这种生长因子对其受体的亲和力没有显著影响,但增加了EGF受体位点的数量。视黄酸对刀豆球蛋白A(Con A)和胰岛素的结合几乎没有影响,这表明类视黄酸对细胞表面糖蛋白的作用具有特异性。用佛波酯12-O-十四烷酰基佛波醇-13-乙酸酯(TPA)和视黄酸处理细胞显示这些化合物对EGF结合的拮抗作用较差。先前已经表明,类维生素A诱导或刺激胚胎癌细胞的分化11 -13。EGF结合可用作监测这些细胞分化的标志物。
Retinoids elicit many biological and biochemical responses from cellsin vitro1–5. One widely used criterion for the responsiveness of cells to retinoids is inhibition of growth; retinoids reduce the saturation density and/or growth rate of many normal and tumorigenic cell lines2,6,7. Propagation of eukaryotic cells has been demonstrated to be dependent on the presence of macromolecular growth factors such as epidermal growth factor (EGF)8–10, which can stimulate proliferation of epithelial and fibroblastic cell lines. We now describe the effect of retinoids on the binding of EGF to its receptor. Retinoic acid enhances binding of125I-labelled EGF to various fibroblastic and epidermal cell lines. It has no marked effect on the affinity of this growth factor for its receptor, but increases the number of EGF receptor sites. Retinoic acid has little effect on the binding of concanavalin A (Con A) and insulin, indicating the specific nature of the action of retinoids on cell-surface glycoproteins. Treatment of cells with the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) and retinoic acid shows poor antagonism between these compounds on EGF binding. It has been previously shown that retinoids induce or stimulate differentiation of embryonal carcinoma cells11–13. EGF binding can be used as a marker to monitor differentiation of these cells.