Insulin/IGF-I hybrid receptors play a major role in IGF-I signaling in thyroid cancer
Insulin/IGF-I hybrid receptors play a major role in IGF-I signaling in thyroid cancer
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DOI：
10.1016/s0300-9084(99)80088-1
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发表时间：
1999-04-01
期刊：
影响因子：
3.9
通讯作者：
Vigneri, R
中科院分区：
文献类型：
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作者：
Belfiore, A;Pandini, G;Vigneri, R
胰岛素样生长因子-I (IGF-I) 在决定多种恶性肿瘤的生物学行为中发挥着重要作用。我们测量了甲状腺癌中的 IGF-I、其受体和相关受体。 IGF-I 存在于正常甲状腺组织和甲状腺癌组织中，它是由基质细胞产生的，而不是由甲状腺细胞产生的。恶性组织中的值显着高于正常组织。与正常值相比，IGF-I 受体 (IGF-I-R) 和同源胰岛素受体 (IR) 在甲状腺癌细胞系 (n = 4) 和样本 (n = 17) 中均过度表达。此外，甲状腺癌标本和细胞系中都存在高水平的混合 IGF-I/胰岛素受体 (IR/IGF-I-R)。 IR/IGF-I-R 杂合体是 14/17 样本中最具代表性的受体类型，并且在所有情况下都超过了 IGF-I-R 含量。杂种含量与IR和IGF-I-R含量相关，表明在甲状腺组织中杂种形成是通过IR和IGF-I-R半受体的随机组装而发生的。 IGF-I 以高亲和力刺激混合受体自身磷酸化。在具有高 IR/IGF-I-Rs 含量的细胞中，针对这些受体的特异性阻断抗体显着抑制 IGF-I 诱导的细胞生长。这些数据表明 IGF-I 系统在甲状腺癌中过度激活，并且 IR/IGF-I-R 杂合受体在这些肿瘤的 IGF-I 有丝分裂信号传导中发挥重要作用。 (C) 法国生物化学和分子生物学公司 / Elsevier，巴黎。
The insulin-like growth factor-I (IGF-I) plays an important role in determining the biological behavior of a variety of malignancies. We measured IGF-I, its receptor and related receptors in thyroid cancer. IGF-I was present both in normal thyroid tissue and in thyroid cancer tissue and it was produced by stromal cells but not by thyrocytes. Values were significantly higher in malignant than in normal tissue. IGF-I receptors (IGF-I-Rs) and the homologous insulin receptors (IRs) were found overexpressed in both thyroid cancer cell lines (n = 4) and specimens (n = 17) as compared to normal values. In addition, high levels of hybrid IGF-I/insulin receptors (IR/IGF-I-Rs) were present in both thyroid cancer specimens and cell lines. IR/IGF-I-R hybrids were the most represented type of receptor in 14/17 specimens and exceeded the IGF-I-R content in all cases. Hybrid content correlated with the IR and IGF-I-R content, suggesting that in thyroid tissue hybrid formation occurs by random assembly of IR and IGF-I-R half receptors. Hybrid receptor autophosphorylation was stimulated by IGF-I with high affinity. In cells with a high IR/IGF-I-Rs content, blocking antibodies specific to these receptors substantially inhibited IGF-I induced cell growth. These data indicate that the IGF-I system is overactivated in thyroid cancer and that IR/IGF-I-R hybrid receptors play an important role in IGF-I mitogenic signaling in these tumors. (C) Societe francaise de biochimie et biologie moleculaire / Elsevier, Paris.