Estrogen induced β-1,4-galactosyltransferase 1 expression regulates proliferation of human breast cancer MCF-7 cells
Estrogen induced β-1,4-galactosyltransferase 1 expression regulates proliferation of human breast cancer MCF-7 cells
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DOI：
10.1016/j.bbrc.2012.08.140
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发表时间：
2012-10-05
影响因子：
3.1
通讯作者：
Ha, Ki-Tae
中科院分区：
文献类型：
--
作者：
Choi, Hee-Jung;Chung, Tae-Wook;Ha, Ki-Tae
β 1,4-半乳糖转移酶1 （B4GALT1）在糖蛋白n链上合成半乳糖-1,4- n -乙酰氨基葡萄糖（Gal β 1- 4glcnac）基团，在许多生物事件中发挥重要作用，包括癌细胞的增殖和迁移。先前的一项微阵列研究报道了该基因在乳腺癌中通过雌激素治疗表达。在这项研究中，我们研究了雌激素诱导的B4GALT1表达的调控机制和生物学功能。我们的数据显示，雌激素诱导的B4GALT1表达定位于细胞内区室和质膜。此外，B4GALT1具有参与Gal β 1-4GlcNAc结构产生的酶活性。启动子实验和染色质免疫沉淀的结果显示，B4GALT1启动子中的3种不同的雌激素反应元件（EREs）对雌激素的反应至关重要。此外，雌激素拮抗剂ICI 182780和er - α - ere结合阻断剂TPBM可抑制雌激素诱导的B4GALT1的表达。然而，抑制与核外通路有关的信号分子，包括g蛋白偶联受体。Ras和丝裂原活化蛋白激酶对B4GALT1的表达无抑制作用。B4GALT1基因的敲除和膜B4GALT1功能的抑制导致雌激素诱导的MCF-7细胞增殖受到显著抑制。考虑到这些结果，我们提出雌激素通过er - α与ERE的直接结合调节B4GALT1的表达，并且表达的B4GALT1通过其作为膜受体的活性在MCF-7细胞的增殖中起着至关重要的作用。(C) 2012爱思唯尔公司版权所有。
Beta 1,4-galactosyltransferase 1 (B4GALT1) synthesizes galactose beta-1,4-N-acetylglucosamine (Gal beta 1-4GlcNAc) groups on N-linked sugar chains of glycoproteins, which play important roles in many biological events, including the proliferation and migration of cancer cells. A previous microarray study reported that this gene is expressed by estrogen treatment in breast cancer. In this study, we examined the regulatory mechanisms and biological functions of estrogen-induced B4GALT1 expression. Our data showed that estrogen-induced expression of B4GALT1 is localized in intracellular compartments and in the plasma membrane. In addition, B4GALT1 has an enzyme activity involved in the production of the Gal beta 1-4GlcNAc structure. The result from a promoter assay and chromatin immunoprecipitation revealed that 3 different estrogen response elements (EREs) in the B4GALT1 promoter are critical for responsiveness to estrogen. In addition, the estrogen antagonists ICI 182,780 and ER-alpha-ERE binding blocker TPBM inhibit the expression of estrogen-induced B4GALT1. However, the inhibition of signal molecules relating to the extra-nuclear pathway, including the G-protein coupled receptors. Ras, and mitogen-activated protein kinases, had no inhibitory effects on B4GALT1 expression. The knock-down of the B4GALT1 gene and the inhibition of membrane B4GALT1 function resulted in the significant inhibition of estrogen-induced proliferation of MCF-7 cells. Considering these results, we propose that estrogen regulates the expression of B4GALT1 through the direct binding of ER-alpha to ERE and that the expressed B4GALT1 plays a crucial role in the proliferation of MCF-7 cells through its activity as a membrane receptor. (C) 2012 Elsevier Inc. All rights reserved.