Monoclonal antibodies against receptor for epidermal growth factor induce early and delayed effects of epidermal growth factor.
Monoclonal antibodies against receptor for epidermal growth factor induce early and delayed effects of epidermal growth factor.
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针对表皮生长因子受体的单克隆抗体诱导表皮生长因子的早期和延迟效应。
DOI：
10.1073/pnas.78.12.7535
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发表时间：
1981
影响因子：
11.1
通讯作者：
Schlessinger,J
中科院分区：
文献类型：
--
作者：
Schreiber,AB;Lax,I;Yarden,Y;Eshhar,Z;Schlessinger,J
用具有异常高数量的表皮生长因子(EGF)膜受体的人表皮样癌细胞(A-431细胞系)免疫小鼠。这些小鼠的脾细胞与NSI细胞融合，NSI细胞是一种不分泌的小鼠骨髓瘤。对获得的杂交瘤细胞分泌的免疫球蛋白进行与A-431细胞的特异性结合筛选，并根据其抑制放射性标记的EGF与A-431细胞膜的结合的能力进行筛选。克隆的杂交系分泌的几种抗体可以抑制放射性标记的EGF与活的A-431细胞、人包皮成纤维细胞和小鼠3T3成纤维细胞的膜受体以及A-431细胞的膜制剂的结合。这些单抗诱导了EGF介导的早期和迟发性生物学效应。与EGF一样，这些抗体诱导了A-431细胞的形态变化，并增强了这些细胞膜上内源性膜蛋白的磷酸化。它们还刺激了人包皮成纤维细胞的DNA合成。这些观察结果支持EGF-受体复合体的生物信息驻留在膜受体的观点。此外，这些抗体为研究EGF受体的结构、加工和作用方式提供了一个强有力的工具。
Mice were immunized with human epidermoid carcinoma cells (A-431 cell line) that possess an unusually high number of membrane receptors for epidermal growth factor (EGF). Spleen cells from these mice were fused with NSI cells, a nonsecreting murine myeloma. The immunoglobulins secreted by the obtained hybridomas were screened for specific binding to A-431 cells and selected according to their ability to inhibit the binding of radiolabeled EGF to the membrane of A-431 cells. Several antibodies secreted by cloned hybrid lines were found to inhibit the binding of radiolabeled EGF to membrane receptors of living A-431 cells, human foreskin fibroblasts, and mouse 3T3 fibroblasts and also to membrane preparations from A-431 cells. These monoclonal antibodies induced the early and delayed biological effects mediated by EGF. Like EGF, the antibodies induced morphological changes in A-431 cells and enhanced the phosphorylation of endogenous membrane proteins in membranes from these cells. They also stimulated DNA synthesis in human foreskin fibroblasts. These observations support the notion that the biological information of the EGF-receptor complex resides in the membrane receptor. Furthermore, the antibodies offer a powerful tool to study the structure, processing, and mode of action of EGF receptors.