Gammeltoft S, Ballotti R, Kowalski A, Westermark B, Van Obberghen E
Department of Clinical Chemistry, Bispebjerg Hospital, Copenhagen, Denmark.
Cancer Res. 1988 Mar 1;48(5):1233-7.
Two types of receptors for insulin-like growth factors (IGFs) were characterized in glioma cell lines established from different human brain tumors of glial origin (astrocytoma grades III and IV) by competitive binding assay, affinity labeling, and protein phosphorylation. Type I IGF receptor is a heterodimer composed of alpha-subunits (Mr 130,000), which bind IGF I and II with equal affinity, and of beta-subunits (Mr 98,000), which show tyrosine kinase activity and autophosphorylation stimulated by IGF I and II with equal potency. The type II IGF binding site is a monomer (Mr 250,000) which binds IGF II with 10 times higher affinity than IGF I. The cellular concentration of type II IGF binding site is about 2- to 5-fold higher than the amount of type I IGF receptor. The characteristics of the two types of IGF receptors in human glioma cell lines are similar to those described recently in fetal rat astrocytes. In contrast the type I IGF receptor in glioma cells is different from that studied previously in normal adult brain regarding the equal affinity for IGF I and II, and the higher molecular size of the alpha-subunit (130,000 versus 115,000). It is suggested that glioma cells may represent a fetal cell type in tumor development of adult human brain. A role of IGF in malignant glioma has not yet been determined, but the presence of IGF receptors is a prerequisite for cellular actions of IGF.
通过竞争性结合试验、亲和标记和蛋白质磷酸化，在源自不同人类胶质源性脑肿瘤（III级和IV级星形细胞瘤）的胶质瘤细胞系中鉴定出两种胰岛素样生长因子（IGF）受体。I型IGF受体是一种异二聚体，由α亚基（分子量130,000）和β亚基（分子量98,000）组成，α亚基以相同亲和力结合IGF I和II，β亚基具有酪氨酸激酶活性，且受IGF I和II刺激时具有同等效力的自磷酸化作用。II型IGF结合位点是一种单体（分子量250,000），其结合IGF II的亲和力比IGF I高10倍。II型IGF结合位点的细胞浓度比I型IGF受体的量高约2至5倍。人类胶质瘤细胞系中这两种IGF受体的特征与最近在胎鼠星形胶质细胞中描述的特征相似。相比之下，胶质瘤细胞中的I型IGF受体在对IGF I和II的同等亲和力以及α亚基更高的分子大小（130,000对115,000）方面与先前在正常成人大脑中研究的不同。有人提出，在成人脑肿瘤发生过程中，胶质瘤细胞可能代表一种胎儿细胞类型。IGF在恶性胶质瘤中的作用尚未确定，但IGF受体的存在是IGF细胞作用的先决条件。
