LEF-1 regulates proliferation and MMP-7 transcription in breast cancer cells
LEF-1 regulates proliferation and MMP-7 transcription in breast cancer cells
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DOI：
10.1111/j.1365-2443.2012.01613.x
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发表时间：
2012-07-01
期刊：
影响因子：
2.1
通讯作者：
Hass, Ralf
中科院分区：
文献类型：
--
作者：
Bucan, Vesna;Mandel, Katharina;Hass, Ralf
基质金属蛋白酶-7（MMP-7）是一种分泌型蛋白水解酶，具有广泛的底物特异性。其表达与包括乳腺癌在内的多种癌症中的肿瘤侵袭、转移和存活相关。利用生物信息学分析，一个保守的LEF-1结合位点变得明显，定位在基因组MMP-7基因座的启动子区域。因此，电泳迁移率变动分析表明，在体外结合LEF-1的预测MMP-7启动子结合位点。在这里，我们证明淋巴增强子结合因子-1（LEF-1）与乳腺癌细胞中增殖相关的细胞周期蛋白D1和MMP-7编码基因的调节有关。因此，使用LEF-1 siRNA降低LEF-1表达分别导致细胞周期蛋白D和MMP-7表达下调。细胞周期分析显示LEF-1 siRNA转染的人乳腺癌细胞明显阻滞于G2/M期。总之，我们的研究结果表明，LEF-1在乳腺癌细胞的增殖和MMP-7转录的调节中发挥着关键作用。
Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with broad substrate specificity. Its expression is associated with tumor invasion, metastasis, and survival in a variety of cancers including breast cancer. Using bioinformatics analysis, a conserved LEF-1 binding site became obvious that is mapped at the promoter region of the genomic MMP-7 locus. Consequently, electrophoretic mobility shift assay demonstrated in vitro binding of LEF-1 to the predicted MMP-7 promoter binding site. Here, we demonstrate that lymphoid enhancer binding factor-1 (LEF-1) is associated with regulation of the proliferation-associated cyclin D1 and a gene encoding MMP-7 in breast cancer cells. Thus, a decrease of LEF-1 expression using LEF-1 siRNA resulted in down-regulation of cyclin D and MMP-7 expression, respectively. Moreover, cell cycle analysis of LEF-1 siRNA-transfected human breast cancer cells revealed a significant arrest in G 2/M phase. Taken together, our results indicate a pivotal role of LEF-1 in the regulation of proliferation and MMP-7 transcription in breast cancer cells.