RECOMBINANT INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1 INHIBITS IGF-I, SERUM, AND ESTROGEN-DEPENDENT GROWTH OF MCF-7 HUMAN BREAST-CANCER CELLS
RECOMBINANT INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1 INHIBITS IGF-I, SERUM, AND ESTROGEN-DEPENDENT GROWTH OF MCF-7 HUMAN BREAST-CANCER CELLS
复制标题
DOI：
10.1002/jcp.1041570204
复制
发表时间：
1993-11-01
影响因子：
5.6
通讯作者：
YEE, D
中科院分区：
文献类型：
--
作者：
FIGUEROA, JA;SHARMA, J;YEE, D
胰岛素样生长因子（IGFs）是乳腺癌细胞的有效丝裂原，其活性受高亲和力结合蛋白（igfbp）的调节。我们最近表明，从人羊水中纯化的IGFBP-1可以中和igf - i依赖性MCF-7细胞的生长。在这项研究中，我们检测了重组IGFBP-1 （rBP-1）对MCF-7细胞的IGF-1、雌二醇（E2）和血清诱导的单层和锚定独立生长（AIG）的影响。在无血清条件下，rBP-1对MCF-7基底单层生长无影响。然而，40 nM rBP-1完全阻断IGF-I和5%木炭剥离血清（CSS）的有丝分裂作用。该浓度的rBP-1部分抑制E2诱导的生长，而80 nM的rBP-1完全抑制E2的有丝分裂性。过量的IGF-I或5nm [Arg3]IGF-I（一种不结合igfbp的物种）的加入抵消了rBP-1的抑制作用。在AIG实验中，与对照组相比，80 nM rBP-1使所有处理组的菌落数量减少至少70%，菌落大小减小。我们检查了rBP-1对IGF-I与MCF-7膜结合和I型IGF受体（IGFR1）激活的影响，发现80 nM rBP-1将IGF-I受体结合降低到非特异性结合水平，并完全消除配体依赖性IGFR磷酸化。然而，5% CSS处理和暴露于E2都不会导致IGFR磷酸化，这表明在这种情况下，不同的机制负责rBP-1抑制作用。我们的数据表明rBP-1可能通过干扰生长因子介导的细胞增殖而作为人类乳腺癌生长的拮抗剂。(C) 1993 Wiley-Liss, Inc。
The insulin-like growth factors (IGFs) are potent mitogens for breast cancer cells and their activity is modulated by high affinity binding proteins (IGFBPs). We have recently shown that IGFBP-1 purified from human amniotic fluid neutralizes IGF-I-dependent growth of MCF-7 cells. In this study we examined the effects of recombinant IGFBP-1 (rBP-1) on IGF-1, estradiol (E2), and serum-induced monolayer and anchorage independent growth (AIG) of MCF-7 cells. Under serum-free conditions, rBP-1 had no effect on MCF-7 basal monolayer growth. However, 40 nM rBP-1 completely blocked the mitogenic action of both IGF-I and 5% charcoal stripped serum (CSS). This concentration of rBP-1 partially inhibited E2-induced growth, while 80 nM rBP-1 completely abolished E2 mitogenicity. The addition of either excess IGF-I or 5 nM [Arg3]IGF-I, a species that does not bind IGFBPs, neutralized rBP-1 inhibitory effects. In AIG assays, 80 nM rBP-1 reduced colony number by at least 70% and decreased colony size in all treatment groups compared to control. We examined rBP-1 effects on both IGF-I binding to MCF-7 membranes and activation of type I IGF receptor (IGFR1) and found that 80 nM rBP-1 reduced IGF-I receptor binding to levels of nonspecific binding and completely abolished ligand-dependent IGFR, phosphorylation. However, neither treatment with 5% CSS nor exposure to E2 resulted in IGFR, phosphorylation suggesting that different mechanism(s) are responsible for rBP-1 inhibitory action under this condition. Our data suggest rBP-1 may serve as an antagonist of human breast cancer growth by interfering with growth factor-mediated cell proliferation. (C) 1993 Wiley-Liss, Inc.