MAGE-D1 inhibits proliferation, migration and invasion of human breast cancer cells

MAGE-D1 inhibits proliferation, migration and invasion of human breast cancer cells
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MAGE-D1抑制人乳腺癌细胞的增殖、迁移和侵袭

DOI:
10.3892/or_00000486
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发表时间:
2009-09-01
期刊:
影响因子:
4.2
通讯作者:
Fang, Wei-Gang
Fang, Wei-Gang
中科院分区:
医学3区
文献类型:
--
作者:
Du, Qiang;Zhang, Yang;Fang, Wei-Gang

文献摘要

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MAGE-D1,也称为 NRAGE 或 Dixin-1,是 MAGE 蛋白家族的成员。它与多个接头相互作用并介导各种细胞功能,例如细胞凋亡、转录、细胞周期、细胞粘附和血管生成的调节。在本研究中,我们评估了MAGE-D1质粒转染对乳腺癌细胞生长、迁移和侵袭的影响。 MTT法和细胞计数一致表明MAGE-D1转染能有效抑制乳腺癌细胞的增殖。然而,进一步的 FACS 分析未能证明 MAGE-D1 转染后细胞周期分布和细胞凋亡发生任何改变。体外划痕伤口愈合试验表明,MAGE-D I 抑制细胞迁移。此外,Boyden小室侵袭实验显示MAGE-D1显着抑制细胞侵袭。此外,为了阐明MAGE-D1抑制细胞生长和侵袭的机制,评估了p53、p21、E-钙粘蛋白、β-连环蛋白、MMP-2和MMP-9的蛋白表达。 Western blotting显示MAGE-D1上调p53、p21和E-cadherin的表达,而下调β-catenin的表达。综上所述,本研究表明MAGE-D1在调节乳腺癌细胞的细胞增殖、迁移和侵袭中发挥重要作用。通过基因转移增强MAGE-D I的表达可以逆转乳腺癌细胞的恶性表型。 MAGE-D1可能是乳腺癌的潜在治疗靶点。
MAGE-D1, also known as NRAGE or Dixin-1, is a member of the MAGE family of proteins. It interacts with multiple adaptors and mediates various cellular functions such as regulation of apoptosis, transcription, cell cycle, cell adhesion and angiogenesis. In this study, we evaluated the effect of MAGE-D1 plasmid transfection on the growth, migration and invasion of breast cancer cells. MTT assay and cell counting consistently showed that MAGE-D1 transfection could effectively inhibit the proliferation of breast cancer cells. However, further FACS analyses failed to demonstrate any alterations in cell cycle distribution and apoptosis after MAGE-D1 transfection. In vitro scratch wound healing assay exhibited that MAGE-D I suppressed cell migration. In addition, Boyden chamber invasion assay showed that MAGE-D1 significantly inhibited cell invasion. Furthermore, in an attempt to elucidate the mechanism of MAGE-D1 in suppressing cellular growth and invasion, the protein expressions of p53, p21, E-cadherin, beta-catenin, MMP-2 and MMP-9 were assessed. Western blotting showed that MAGE-D1 upregulated the expression of p53, p21 and E-cadherin, whereas down-regulated beta-catenin expression. Taken together, this study suggests that MAGE-D1 play important roles in the regulation of cell proliferation, migration and invasion of breast cancer cells. Enhanced expression of MAGE-D I by gene transfer could reverse the malignant phenotypes of breast cancer cells. MAGE-D1 may be a potential therapeutic target for breast cancer.