Li B D, Khosravi M J, Berkel H J, Diamandi A, Dayton M A, Smith M, Yu H
Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Int J Cancer. 2001 Mar 1;91(5):736-9. doi: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1111>3.0.co;2-#.
Insulin-like growth factor-I (IGF-I) has mitogenic and anti-apoptotic effects on breast cancer cells. Epidemiologic studies have shown that high plasma levels of IGF-I and low levels of IGF binding protein (BP)-3 are associated with increased risk of breast cancer in premenopausal women. The actions of IGF-I are mediated through the IGF-I receptor (IGF-IR) and are regulated by IGFBPs. In circulation, most of the IGF-I binds to IGFBP-3, and binding of IGF-I to IGFBP-3 inhibits the actions of IGF-I. Since free IGF-I, which does not bind to IGFBPs, can readily cross the endothelial barrier to interact with IGF-IR, circulating free IGF-I is thought to be more relevant to the biologic activity of IGF-I. To examine the association of free IGF-I with breast cancer, we compared free IGF-I levels between 40 newly diagnosed breast cancer patients and 40 age- and race-matched healthy controls. Plasma levels of free IGF-I, total IGF-I and IGF-II, as well as total, intact and fragment IGFBP-3, were measured using commercial immunoassay kits. The association between IGF-I and breast cancer was examined using the conditional logistic regression analysis. Analysis of correlation (Spearman) showed that free IGF-I was correlated with total IGF-I and IGFBP-3 but not with IGF-II. The odds ratios for breast cancer patients having high plasma IGF-I (> or = median) after adjusting for menopausal status and IGFBP-3 were 2.00 (p < o r = 0.376) for total IGF-I and 6.31 (p < or = 0.047) for free IGF-I. A high ratio of IGF-I to IGFBP-3 was also associated with breast cancer (p < 0.05). No association was found for IGF-II, nor for total, intact and fragment IGFBP-3. The findings of this study suggest that measuring free IGF-I in circulation is more useful than measuring total IGF-I with respect to evaluation of an association between IGF-I and breast cancer risk.
胰岛素样生长因子-I（IGF-I）对乳腺癌细胞具有促有丝分裂和抗凋亡作用。流行病学研究表明，绝经前女性血浆中IGF-I水平升高及胰岛素样生长因子结合蛋白（BP）-3水平降低与乳腺癌风险增加相关。IGF-I的作用通过IGF-I受体（IGF-IR）介导，并受胰岛素样生长因子结合蛋白调节。在循环中，大部分IGF-I与IGFBP-3结合，IGF-I与IGFBP-3的结合会抑制IGF-I的作用。由于未与胰岛素样生长因子结合蛋白结合的游离IGF-I能够轻易穿过内皮屏障与IGF-IR相互作用，因此循环中的游离IGF-I被认为与IGF-I的生物学活性更为相关。为了研究游离IGF-I与乳腺癌的关联，我们比较了40例新诊断乳腺癌患者与40例年龄和种族匹配的健康对照者的游离IGF-I水平。使用商用免疫分析试剂盒测量血浆中游离IGF-I、总IGF-I和IGF-II水平，以及总、完整和片段化的IGFBP-3水平。采用条件逻辑回归分析研究IGF-I与乳腺癌之间的关联。相关性分析（Spearman）显示，游离IGF-I与总IGF-I和IGFBP-3相关，但与IGF-II无关。在调整绝经状态和IGFBP-3后，血浆IGF-I水平高（≥中位数）的乳腺癌患者的比值比，总IGF-I为2.00（p≤0.376），游离IGF-I为6.31（p≤0.047）。IGF-I与IGFBP-3的高比值也与乳腺癌相关（p<0.05）。未发现IGF-II以及总、完整和片段化的IGFBP-3与乳腺癌有关联。本研究结果表明，就评估IGF-I与乳腺癌风险之间的关联而言，测量循环中的游离IGF-I比测量总IGF-I更有用。
