Thompson D M, Gill G N
Department of Medicine, University of California, San Diego, School of Medicine, La Jolla 92093.
Cancer Surv. 1985;4(4):767-88.
Retroviral onc genes are derived from cellular proto-oncogenes that may function in normal cellular growth control. The epidermal growth factor (EGF) receptor is the proto-oncogene of erbB; both possess intrinsic protein tyrosine kinase activity, a property shared by several retroviral onc genes. The EGF receptor is a transmembrane glycoprotein with an external EGF binding domain and a cytoplasmic region that is homologous with other tyrosine kinases. erbB lacks the EGF binding and carboxyl terminal regions, which are thought to be important in regulation. The EGF receptor is regulated by several mechanisms: stimulation by ligand binding and self-phosphorylation, inhibition by heterologous phosphorylation and downregulation by ligand. EGF binding stimulates several early events, including phosphatidylinositol (PI) turnover in A431 cells. A PI kinase activity copurifies with the EGF receptor and some other tyrosine kinases, but this is a contaminant as it can be separated from the EGF receptor. Although the role of proto-onc genes in human malignancy is incompletely defined, increased numbers of EGF receptors are present in several types of human tumours. Overexpression of EGF receptors, as occurs in human epidermoid carcinoma A431 cells, can augment cell growth because of increased formation of active ligand:receptor complexes. Gene amplification is the mechanism underlying overexpression of EGF receptors in A431 cells and in some glioblastoma multiforme tumours.
逆转录病毒致癌基因源自可能在正常细胞生长控制中发挥作用的细胞原癌基因。表皮生长因子（EGF）受体是erbB的原癌基因；两者都具有内在的蛋白酪氨酸激酶活性，这是几种逆转录病毒致癌基因共有的特性。EGF受体是一种跨膜糖蛋白，具有外部EGF结合结构域和与其他酪氨酸激酶同源的细胞质区域。erbB缺乏EGF结合区和羧基末端区域，这些区域被认为在调节中很重要。EGF受体受多种机制调节：通过配体结合和自身磷酸化进行刺激，通过异源磷酸化进行抑制，以及通过配体进行下调。EGF结合刺激多种早期事件，包括A431细胞中的磷脂酰肌醇（PI）周转。一种PI激酶活性与EGF受体和其他一些酪氨酸激酶共纯化，但这是一种污染物，因为它可以与EGF受体分离。尽管原癌基因在人类恶性肿瘤中的作用尚未完全明确，但在几种类型的人类肿瘤中存在数量增加的EGF受体。如在人类表皮样癌A431细胞中发生的那样，EGF受体的过表达可由于活性配体：受体复合物形成增加而增强细胞生长。基因扩增是A431细胞和一些多形性胶质母细胞瘤肿瘤中EGF受体过表达的潜在机制。
