积极的和消极的芳香化酶表达的转录调控在人类乳腺癌组织。

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积极的和消极的芳香化酶表达的转录调控在人类乳腺癌组织。

95年5月,J类固醇生物化学杂志。2005 (1 - 5):17-23。

PubMed ID

15955695 (在PubMed

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通过执行primer-specific rt - pcr分析,三个实验室包括我们发现外显子I.3和PII是两个主要的外显子存在于芳香化酶mrna隔绝乳腺肿瘤。这些结果表明,推动者I.3和二世的主要推动者是导演芳香化酶表达在乳腺肿瘤。描述的转录因子与启动子附近的两个元素交互I.3二世,即。S1和CREaro,帮助我们更好地理解机制启动子的开关使用正常乳腺组织和癌组织之间。两个监管区域的位置被DNase我足迹和DNA删除映射分析。我们应用酵母一个杂化的方法来筛选人类乳腺组织混合cDNA表达文库基因编码的蛋白质绑定到这些地区。我们的研究结果表明,在正常乳腺组织,推动者I.3和II的作用是抑制通过绑定EAR-2, COUP-TFI, RARgamma S1,和通过蜗牛和蛞蝓的绑定蛋白结合位点,淬灭了CREaro活动。EAR-2癌组织的表达水平,COUP-TF1, EARgamma、蜗牛、蛞蝓减少,芳香化酶表达然后向上调节通过绑定ERRalpha S1和CREaro CREB1或相关因素的结合。在另一项研究中,我们发现,雌激素可以调控的芳香化酶表达在乳腺癌细胞non-genomic ERalpha作用与经济增长通过相声factor-mediated通路。我们的初步结果表明,蛋白激酶C三角洲参与这个ERalpha-growth因子介导的监管。 To further understand the regulatory mechanism, we have recently initiated an in vivo footprinting analysis of the -260/+76 bp region of promoter I.3. The experiments were conducted with both MCF-7 and MDA-MB-231 breast cancer cells. Our results revealed several footprinted sites. Five regions (sites 1-5) were then selected for functional analysis through DNA site-directed mutagenesis experiments. This analysis has also confirmed the promoter I.3 TATA site and Snail/Slug binding site. These mutants showed higher luciferase activity when compared to the wild-type, indicating that the proteins binding to these sites were acting as repressors. By reviewing findings from our laboratory and other laboratories, a detailed mechanism for the transcriptional regulation of aromatase expression in breast cancer tissue is summarized and discussed.

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药物靶点

药物	目标	类	生物	药理作用	行动
染料木黄酮	类固醇激素受体ERR1	蛋白质	人类	未知的	受体激动剂	细节