Insulin-like growth factors and cancer.
Insulin-like growth factors and cancer.
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DOI：
10.1038/bjc.1992.65
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发表时间：
1992-03
影响因子：
8.8
通讯作者：
Macaulay, V M
中科院分区：
文献类型：
--
作者：
Macaulay, V M
胰岛素样生长因子（IGF）。也称为生长调节素，是过去 30 年进行的三项独立研究的结果（Van Wyk & Underwood，1978）。首先，IGF 促进 35-硫酸盐掺入软骨，从而形成“硫酸化”因子（Salmon & Daughaday，1957）。其次，它们介导血清（Pierson & Temin，1972）和大鼠肝细胞条件培养基（增殖刺激活性，MSA；Dulak & Temin. 1973）的促有丝分裂活性。第三。 IGF 具有不受抗胰岛素抗体抑制的胰岛素样活性（非抑制性胰岛素样活性，NSILA：Froesch 等，1963）。序列分析表明，这些功能由两种主要肽发挥作用：IGF-I，也称为生长调节素-C（Klapper 等，1983）和 IGF-II。其中大鼠形式是 MSA（Rinderknecht & Humbel. 1978；Marquardt et al. 1981）。 IGF 术语现在已成为首选，因为 IGF-II 没有生长调节素名称（Daughaday 等，1987）。IGF-I（70 个残基，MW 7649）和 IGF-II（67 个残基，MW 7471）是单链肽，具有约 70% 的序列同源性，与胰岛素原具有 50% 同源性。成熟IGF具有与胰岛素原同源性最高的A和B结构域，以及与胰岛素原没有序列同源性的C肽结构域。和羧基末端 D 结构域（Daughaday & Rotwein. 1989）。 IGF-I 基因位于染色体 12q 上，IGF-II 基因位于染色体 11p 上，与胰岛素基因相邻 (Barreca & Minuto. 1989)。在小鼠体内，IGF-II 基因被印记。那是。母本基因和父本基因的表达存在差异。具体而言，父系 IGF-II 基因具有活性（Willison. 1991）。 IGF-I 由肝脏合成，也由包括肾和肺在内的其他内脏合成（D'Ercole 等，1984）。肝脏合成在很大程度上决定了血清水平，受到生长激素 (GH) 的调节，并且还随肝功能和营养状况而变化（Underwood 等，1986；Zapf 和 Froesch。1986）。在内分泌敏感组织中。 IGF-I 基因表达可能受 GH 以外的激素调节。值得注意的是，在大鼠子宫中，IGF-I 表达被雌激素增强，并被 GH 轻微抑制（Murphy & Friesen，1988）。在体外，IGF-I 是正常细胞（包括软骨细胞和其他间充质衍生物）的有效有丝分裂原（Clemmons & Van Wyk，1981）。在体内，IGF-I 对脂肪组织、肌肉和肝脏具有急性胰岛素样合成代谢作用（Zapf & Froesch，1986；Guler 等人，1987）。然而，其最重要的生理作用是作为生长的主要调节剂，尤其是包括骨和软骨在内的间充质组织（Schoenle 等，1982；Van Buul-Offers 等，1986；Mathews 等，1988）。 IGF-II在实验上具有代谢和促有丝分裂作用，但其生理功能尚不清楚。血清浓度对 GH 的依赖性较小。它会导致垂体切除动物的生长促进作用减弱（Schoenle et al., 1983）。 IGF-II mRNA 在间质来源的胎儿组织中表达，包括肾、肝
The insulin-like growth factors (IGFs). also known as somatomedins, have been identified as a result of three separate lines of research carried out over the last 30 years (Van Wyk & Underwood, 1978). First, IGFs promote incorporation of 35-sulphate into cartilage, hence'sulphation'factor (Salmon & Daughaday, 1957). Secondly, they mediate the mitogenic activity of serum (Pierson & Temin, 1972) and medium conditioned by rat hepatocytes (multiplication stimulating activity, MSA; Dulak & Temin. 1973). Thirdy. IGFs have insulin-like activity which is not inhibited by anti-insulin antibodies (non-suppressive insulin-like activity, NSILA: Froesch et al., 1963). Sequence analysis revealed that these functions are subserved by two main peptide: IGF-I, also known as somatomedin-C (Klapper et al.. 1983) and IGF-II. of which the rat form is MSA (Rinderknecht & Humbel. 1978; Marquardt et al.. 1981). The IGF terminology is now preferred as there is no somatomedin designation for IGF-II (Daughaday et al.. 1987).IGF-I (70 residues, MW 7649) and IGF-II (67 residues. MW 7471) are single chain peptides with around 70% sequence homology, and 50% homology with pro-insulin. Mature IGFs have A and B domains where the homology with proinsulin is highest, a C-peptide domain which has no sequence homology with proinsulin. and a carboxyterminal D domain (Daughaday & Rotwein. 1989). The IGF-I gene is located on chromosome 12q, and the IGF-II gene is on chromosome llp, contiguous with the insulin gene (Barreca & Minuto. 1989). In the mouse, the IGF-II gene is imprinted. that is. there is a difference in expression between the maternal and paternal genes. Specifically, it is the paternal IGF-II gene which is active (Willison. 1991). IGF-I is synthesised by the liver and also by other viscera including kidney and lung (D'Ercole et al., 1984). Hepatic synthesis, which largely determines serum levels, is regulated by growth hormone (GH) and also varieswith liver function and nutritional status (Underwood et al., 1986; Zapf & Froesch. 1986). In endocrine-sensitive tissues. IGF-I gene expression may be regulated by hormones other than GH. Notably in rat uterus, IGF-I expression is enhanced by oestrogen, and is repressed to a small extent by GH (Murphy & Friesen, 1988). In vitro, IGF-I is a potent mitogen for normal cells including chondrocytes and other mesenchymal derivatives (Clemmons & Van Wyk, 1981). In vivo, IGF-I has acute insulin-like anabolic effects on adipose tissue, muscle and liver (Zapf & Froesch, 1986; Guler et al.. 1987). However its most important physiological role is as the primary regulator of growth, especially of mesenchymal tissues including bone and cartilage (Schoenle et al., 1982; Van Buul-Offers et al.. 1986; Mathews et al., 1988). IGF-II has metabolic and mito-genic effects experimentally, but its physiological function is unclear. Serum concentrations are less dependent on GH. and it causes less growth promotion in hypophysectomised animals (Schoenle et al., 1983). IGF-II mRNA is expressed in foetal tissues of mesenchymal origin, including kidney, liver