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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >MTA1, a transcriptional activator of breast cancer amplified sequence 3
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MTA1, a transcriptional activator of breast cancer amplified sequence 3

机译：MTA1，乳腺癌的转录激活因子，扩增序列3

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摘要

Here we define a function of metastasis-associated protein 1 (MTA1), a presumed corepressor of estrogen receptor alpha (ER alpha), as a transcriptional activator of Breast Cancer Amplified Sequence 3 (BCAS3), a gene amplified and overexpressed in breast cancers. We identified BCAS3 as a MTA1 chromatin target in a functional genomic screen. MTA1 stimulation of BCAS3 transcription required ERa and involved a functional ERE half-site in BCAS3. Furthermore, we discovered that MTA1 is acetylated on lysine 626, and that this acetylation is necessary for a productive transcriptional recruitment of RNA polymerase 11 complex to the BCAS3 enhancer sequence. BCAS3 expression was elevated in mammary tumors from MTA1 transgenic mice and 60% of the human breast tumors, and correlated with the coexpression of MTA1 as well as with tumor grade and proliferation of primary breast tumor samples. These findings reveal a previously unrecognized function of MTA1 in stimulating BCAS3 expression and suggest an important role for MTA1-BCAS3 pathway in promoting cancerous phenotypes in breast tumor cells.
机译：在这里，我们定义了一种与转移相关的蛋白1（MTA1）的功能，它是雌激素受体α（ER alpha）的推定核心抑制剂，作为乳腺癌扩增序列3（BCAS3）的转录激活因子，该基因在乳腺癌中被扩增和过度表达。我们在功能性基因组筛选中将BCAS3确定为MTA1染色质靶标。 MTA1刺激BCAS3转录需要ERa，并涉及BCAS3中一个功能性ERE半位点。此外，我们发现MTA1在赖氨酸626上被乙酰化，并且这种乙酰化对于RNA聚合酶11复合物向BCAS3增强子序列的有效转录募集是必需的。在MTA1转基因小鼠和60％的人类乳腺肿瘤的乳腺肿瘤中BCAS3表达升高，并且与MTA1的共表达以及原发性乳腺肿瘤样品的肿瘤分级和增殖相关。这些发现揭示了MTA1在刺激BCAS3表达方面以前无法认识的功能，并暗示MTA1-BCAS3途径在促进乳腺肿瘤细胞癌表型中起重要作用。

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