INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN ENHANCEMENT OF INSULIN-LIKE GROWTH FACTOR-I (IGF-I)-MEDIATED DNA-SYNTHESIS AND IGF-I BINDING IN A HUMAN BREAST-CARCINOMA CELL-LINE
INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN ENHANCEMENT OF INSULIN-LIKE GROWTH FACTOR-I (IGF-I)-MEDIATED DNA-SYNTHESIS AND IGF-I BINDING IN A HUMAN BREAST-CARCINOMA CELL-LINE
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DOI：
10.1002/jcp.1041580110
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发表时间：
1994-01-01
影响因子：
5.6
通讯作者：
FONTANA, JA
中科院分区：
文献类型：
--
作者：
CHEN, JC;SHAO, ZM;FONTANA, JA
胰岛素样生长因子(IGF)是恶性细胞增殖的强效促进剂。大多数分泌的IGF与大量细胞分泌的特定的IGF结合蛋白(IGFBPs)结合。这些蛋白质可以抑制或增强IGF的作用。乳腺癌细胞分泌多种IGFBPs。我们先前已经证明，维甲酸(RA)抑制IGF-1刺激的MCF-7细胞的增殖与条件培养液中IGFBP-3水平的增加有关。因此，我们研究了重组IGFBP-3以及IGFBP-2、-4和-5对IGF-I刺激MCF-7人乳腺癌细胞DNA合成和IGF-I结合的影响。IGFBP-2和-3增强IGF-I对MCF-7细胞DNA合成的刺激作用，而IGFBP-4和-5则无此作用。用IGFBP-3表达载体转染MCF-7细胞后，IGFBP-3的分泌增加，IGF-I结合增加，细胞增殖增加。转染对照pSVneo的MCF-7细胞经IGF-I预先孵育后，IGF-I对胸腺嘧啶核苷掺入的进一步刺激作用不明显，而IGFBP-3可继续刺激[H-3]-胸腺嘧啶核苷掺入，提示IGFBP-3对IGF-1介导的胸腺嘧啶核苷受体下调具有保护作用。因此，MCF-7细胞分泌的IGFBP-3可以增强IGF-I对DNA合成的刺激作用，增加IGF-I与这些细胞的结合，并阻止IGF-I诱导的自身受体脱敏，提示IGFBP-3在IGF-I介导的乳腺癌增殖中起重要作用。(C)1994年Wiley-Liss，Inc.
The insulin-like growth factors (IGFs) are potent milogens for malignant cell proliferation. The majority of secreted IGFs are bound to specific IGF-binding proteins (IGFBPs) that are secreted by a large number of cells. These proteins may either inhibit or enhance IGF actions. Breast carcinoma cells secrete a variety of IGFBPs. We have previously demonstrated that retinoic acid (RA) inhibition of IGF-1-stimulated MCF-7 cell proliferation is associated with increased IGFBP-3 levels in the conditioned media. We therefore investigated the effect of recombinant IGFBP-3 as well as IGFBP-2, -4 and -5 on IGF-I stimulation of DNA synthesis and IGF-I binding in the MCF-7 human breast carcinoma cell line. IGFBP-2 and -3 enhanced IGF-I stimulation of DNA synthesis in MCF-7 cells while IGFBP-4 and -5 had no effect. Transfection of MCF-7 cells with an IGFBP-3 expression vector resulted in the enhanced secretion of IGFBP-3 with an accompanying increase in IGF-I binding as well as increased cell proliferation upon treatment of the cells with IGF-I. IGF-I preincubation of MCF-7 cells transfected with control pSVneo plasmids results in cells refractory to further IGF-I stimulation of thymidine incorporation while IGF-I continues to stimulate [H-3]-thymidine incorporation in IGFBP-3-transfected MCF-7 cells, suggesting that IGFBP-3 protects the cells from IGF-1-mediated down regulation of its receptor. Therefore, IGFBP-3 secreted by MCF-7 cells can enhance IGF-I stimulation of DNA synthesis, increase IGF-I binding to these cells, and prevent IGF-I-induced desensitization of its own receptor, suggesting that IGFBP-3 plays a significant role in IGF-I-mediated breast carcinoma proliferation. (C) 1994 Wiley-Liss, Inc.