Estrogen and insulin/IGF-1 cooperatively stimulate cell cycle progression in MCF-7 breast cancer cells through differential regulation of c-Myc and cyclin D1
Estrogen and insulin/IGF-1 cooperatively stimulate cell cycle progression in MCF-7 breast cancer cells through differential regulation of c-Myc and cyclin D1
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DOI：
10.1016/j.mce.2004.08.002
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发表时间：
2005-01-14
影响因子：
4.1
通讯作者：
Sarcevic, B
中科院分区：
文献类型：
--
作者：
Mawson, A;Lai, A;Sarcevic, B
雌激素和胰岛素/胰岛素样生长因子-I（IGF-I）是乳腺上皮细胞的主要有丝分裂原，当共同给药时，协同诱导G（1）-S期细胞周期进展。我们通过评估关键的细胞周期调节因子来研究这种协同性。c-Myc和细胞周期蛋白D1代表MCF-7乳腺癌细胞中这些有丝分裂原作用的会聚点。这些研究表明，雌激素显着增加c-Myc和细胞周期蛋白D1蛋白，而胰岛素主要增加细胞周期蛋白D1水平。c-Myc和细胞周期蛋白D1的这种累积增加有助于这些促有丝分裂原的协同作用，因为c-Myc或细胞周期蛋白D1的异位表达与雌激素或胰岛素信号传导途径协同作用以增加细胞周期进程。MAPK或PI 3-激酶通路的抑制显著降低了c-Myc和细胞周期蛋白D1的蛋白水平和细胞周期进程。细胞周期蛋白D1的异位表达部分克服了这种抑制，而c-Myc的异位表达部分克服了MAPK，但没有PI 3-激酶抑制。因此，雌激素和胰岛素/IGF-1差异调节c-Myc和细胞周期蛋白D1协同刺激乳腺癌细胞增殖。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Estrogen and insulin/insulin-like growth factor-I (IGF-I) are major mitogens for breast epithelial cells and when co-administered, synergistically induce G(1)-S phase cell cycle progression. We investigated this cooperativity by evaluating if the key cell cycle regulators. c-Myc and cyclin D1, represent points of convergence in the action of these mitogens in MCF-7 breast cancer cells. These studies demonstrated that estrogen significantly increased both c-Myc and cyclin D1 protein, while insulin predominantly increased cyclin D1 levels. This cumulative increase in c-Myc and cyclin D1 contributes to the cooperativity of these mitogens, since ectopic expression of c-Myc or cyclin D1 cooperates with either the estrogen Or insulin signaling pathways to increase cell cycle progression. Inhibition of the MAPK or PI3-kinase pathway significantly reduced c-Myc and cyclin D1 protein levels and cell cycle progression. Ectopic expression of cyclin D1 partially overcame this inhibition, while ectopic expression of c-Myc partially overcame MAPK but not PI3-kinase inhibition. Therefore, estrogen and insulin/IGF-1 differentially regulate c-Myc and cyclin D1 to cooperatively stimulate breast cancer cell proliferation. (C) 2004 Elsevier Ireland Ltd. All rights reserved.