Burger Angelika M, Leyland-Jones Brian, Banerjee Kris, Spyropoulos Demetri D, Seth Arun K
Laboratory of Molecular Pathology, Department of Anatomic Pathology and Division of Molecular and Cellular Biology, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ont., Canada.
Eur J Cancer. 2005 Jul;41(11):1515-27. doi: 10.1016/j.ejca.2005.04.023.
Insulin and insulin-like growth factors (IGFs) have critical functions in growth regulatory signalling pathways. They are part of a tightly controlled network of ligands, receptors, binding proteins and their proteases. However, the system becomes uncontrolled in neoplasia. The insulin-like growth factor binding protein 3 (IGFBP-3) and the insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) have unique properties among the sixteen known members of the IGFBP superfamily. IGFBP-3 has very high affinity for IGFs (k(d) approximately 10(-10) M), it transports >75% of serum IGF-I and -II, whereas it's affinity for insulin is very low. On the other hand, IGFBP-rP1 binds insulin with very high affinity (500-fold higher compared to other IGFBPs), but has low affinity for IGF-I and -II proteins (k(d) = 3 x 10(-8) M). In this review, we have examined the roles of IGFBP-3 and IGFBP-rP1 in breast cancer, and discuss the potential impact of these two proteins in mammary carcinoma risk assessment and the development of treatments for breast cancer.
胰岛素和胰岛素样生长因子（IGFs）在生长调节信号通路中发挥着关键作用。它们是由配体、受体、结合蛋白及其蛋白酶组成的严格控制网络的一部分。然而，该系统在肿瘤形成过程中会失去控制。胰岛素样生长因子结合蛋白3（IGFBP - 3）和胰岛素样生长因子结合蛋白相关蛋白1（IGFBP - rP1）在IGFBP超家族的16个已知成员中具有独特的性质。IGFBP - 3对IGFs具有非常高的亲和力（解离常数k(d)约为10(-10) M），它运输血清中>75%的IGF - I和 - II，而它对胰岛素的亲和力非常低。另一方面，IGFBP - rP1对胰岛素具有非常高的亲和力（与其他IGFBPs相比高500倍），但对IGF - I和 - II蛋白的亲和力较低（k(d) = 3 x 10(-8) M）。在本综述中，我们研究了IGFBP - 3和IGFBP - rP1在乳腺癌中的作用，并讨论了这两种蛋白在乳腺癌风险评估和治疗开发中的潜在影响。
