Insulin-like growth factor binding protein-3 induces apoptosis in MCF7 breast cancer cells
Insulin-like growth factor binding protein-3 induces apoptosis in MCF7 breast cancer cells
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DOI：
10.1006/bbrc.1997.7089
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发表时间：
1997-08-28
影响因子：
3.1
通讯作者：
Pollak, M
中科院分区：
文献类型：
--
作者：
Nickerson, T;Huynh, H;Pollak, M
已知胰岛素样生长因子（IGFs）具有有效的抗凋亡活性。抗雌激素ICI 182，780（ICI）是MCF 7人乳腺癌细胞生长的有效抑制剂，并且最近报道其部分地通过上调胰岛素样生长因子结合蛋白（IGFBP）-3和-5的表达而作为抗增殖剂，所述IGFBP-3和-5在许多实验系统中减弱IG的生物活性。我们在这里显示ICI和IGFBP-3诱导MCF 7细胞凋亡。用10 nM ICI或36 nM重组人IGFBP-3处理MCF 7细胞72小时使细胞凋亡相对于对照增加了3.5倍，如通过测量DNA片段化的细胞死亡ELISA所定量的。长R-3 IGF-I是一种IGF-I类似物，对IGFBP的亲和力大大降低，但对IGF-I受体的亲和力相似，是比IGF-I更有效的IGFBP-3诱导和ICI诱导的细胞凋亡抑制剂。这些结果表明IGFBP-3通过降低IGF-I受体配体的生物利用度来增强细胞凋亡，并表明ICI对IGFBP-3表达的调节有助于该化合物诱导的细胞凋亡。更一般地，数据表明IGFBPs是细胞凋亡的调节剂。(C)北京：科学出版社.
Insulin-like growth factors (IGFs) are known to have potent antiapoptotic activity. The antiestrogen ICI 182,780 (ICI) is a potent inhibitor of MCF7 human breast cancer cell growth and has recently been reported to act as an antiproliferative agent in part via upregulation of expression of insulin-like growth factor binding proteins (IGFBPs) -3 and -5, which attenuate the bioactivity of IG;Bs in many experimental systems. We show here that ICI and IGFBP-3 induce apoptosis in MCF7 cells. Treatment of MCF7 cells with 10 nM ICI or 36 nM recombinant human IGFBP-3 for 72 hours increased apoptosis similar to 3.5-fold relative to control as quantitated by a cell death ELISA which measures DNA fragmentation. Long R-3 IGF-I, an IGF-I analogue with greatly reduced affinity for IGFBPs yet similar affinity for IGF-I receptors, was a more potent inhibitor of IGFBP-3-induced and ICI-induced apoptosis than IGF-I. These results suggest that IGFBP-3 enhances apoptosis by reducing bioavailability of ligands for the IGF-I receptor and suggest that modulation of IGFBP-3 expression by ICI contributes to apoptosis induced by this compound. More generally, the data suggest that IGFBPs are regulators of apoptosis. (C) 1997 Academic Press.