Hormonal regulation of metastasis-associated protein 3 transcription in breast cancer cells
Hormonal regulation of metastasis-associated protein 3 transcription in breast cancer cells
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DOI：
10.1210/me.2004-0258
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发表时间：
2004-12-01
影响因子：
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通讯作者：
Wade, PA
中科院分区：
文献类型：
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作者：
Fujita, N;Kajita, M;Wade, PA
转移相关蛋白3 （MTA3）是Mi-2/NuRD转录辅抑制因子复合物的细胞类型特异性亚基。在乳腺癌细胞中，MTA3和Mi-2/NuRD复合物介导蜗牛转录因子的抑制，蜗牛转录因子促进上皮细胞向间质细胞的转化。因此，MTA3在乳腺癌中起维持分化上皮状态的作用。有趣的是，在乳腺上皮细胞中，MTA3的生物合成需要功能性雌激素受体（ER）和雌二醇。在这里，我们研究了乳腺癌细胞中雌激素和er依赖性MTA3表达的分子基础。利用瞬时转染法对MTA3启动子进行分子解剖，发现了一个高水平转录所需的复合元件，该元件由SP1位点组成，靠近雌激素反应元件半位点。在多种乳腺癌细胞系中，通过RNA干扰导致SP1或er - α缺失导致MTA3转录物缺失，表明内源性MTA3表达需要这两种转录因子。因此，MTA3基因加入了由SP1和ER共同调控的不断增长的基因座列表。
Metastasis-associated protein 3 (MTA3) is a cell type-specific subunit of the Mi-2/NuRD transcriptional corepressor complex. In breast cancer cells, MTA3 and the Mi-2/NuRD complex mediate repression of Snail, a transcription factor that promotes epithelial to mesenchymal transitions. Thus, MTA3 functions to maintain a differentiated, epithelial status in breast cancer. Interestingly, in mammary epithelial cells, MTA3 biosynthesis requires both functional estrogen receptor ( ER) and estradiol. Here we have investigated the molecular basis for estrogen and ER-dependent expression of MTA3 in breast cancer cells. Molecular dissection of the MTA3 promoter using transient transfection assays identified a composite element required for high-level transcription consisting of an SP1 site in close proximity to a consensus estrogen response element half-site. Depletion of either SP1 or ER-alpha by RNA interference led to loss of MTA3 transcript in multiple breast cancer cell lines, indicating a requirement for both transcription factors in expression of endogenous MTA3. The MTA3 gene thus joins a growing list of loci regulated by both SP1 and ER.