Estradiol Represses the GD3 Synthase Gene ST8SIA1 Expression in Human Breast Cancer Cells by Preventing NFκB Binding to ST8SIA1 Promoter
Estradiol Represses the GD3 Synthase Gene ST8SIA1 Expression in Human Breast Cancer Cells by Preventing NFκB Binding to ST8SIA1 Promoter
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DOI：
10.1371/journal.pone.0062559
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发表时间：
2013-04-23
期刊：
影响因子：
3.7
通讯作者：
Delannoy, Philippe
中科院分区：
文献类型：
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作者：
Bobowski, Marie;Vincent, Audrey;Delannoy, Philippe
最近的数据强调了G（D3）合酶（GD 3S）和复杂的神经节苷脂在雌激素受体（ER）阴性乳腺癌进展中的可能作用。在这里，我们描述了主要的GD 3S编码基因ST 8 SIA 1在乳腺肿瘤中表达的转录。我们表征了Hs 578 T乳腺癌细胞中相应的核心启动子，并表明雌二醇降低了ER阳性MCF-7细胞和ER α转染的ER阴性Hs 578 T细胞中ST 8 SIA 1 mRNA的表达。ST 8 SIA 1的核心启动子序列的活性也被雌二醇抑制。ST 8 SIA 1的核心启动子含有两个推定的雌激素反应元件（ERE），没有发现参与启动子活性途径。然而，NF κ B B参与了ST 8 SIA 1的转录激活，我们证明雌二醇通过抑制p65和p50核定位来阻止NF κ B B与ER α表达乳腺癌细胞中的ST 8 SIA 1核心启动子结合。雌激素受体阴性肿瘤中NF-κ B B通路的激活，由于缺乏雌二醇信号传导，可能解释了G（D3）合酶在该肿瘤亚型中的过度表达。
Recent data have underlined a possible role of G(D3) synthase (GD3S) and complex gangliosides in Estrogen Receptor (ER) negative breast cancer progression. Here, we describe the main transcript of the GD3S coding gene ST8SIA1 expressed in breast tumors. We characterized the corresponding core promoter in Hs578T breast cancer cells and showed that estradiol decreases ST8SIA1 mRNA expression in ER-positive MCF-7 cells and ER alpha-transfected ER-negative Hs578T cells. The activity of the core promoter sequence of ST8SIA1 is also repressed by estradiol. The core promoter of ST8SIA1 contains two putative Estrogen Response Elements (ERE) that were not found to be involved in the promoter activity pathway. However, NF kappa B was shown to be involved in ST8SIA1 transcriptional activation and we demonstrated that estradiol prevents NF kappa B to bind to ST8SIA1 core promoter in ER alpha expressing breast cancer cells by inhibiting p65 and p50 nucleus localization. The activation of NF kappa B pathway in ER-negative tumors, due to the absence of estradiol signaling, might explain the overexpression of G(D3) synthase in this tumor subtype.