Regulation of DNA replication fork genes by 17β-estradiol
Regulation of DNA replication fork genes by 17β-estradiol
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DOI：
10.1210/me.16.6.1215
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发表时间：
2002-06-01
影响因子：
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通讯作者：
Afshari, CA
中科院分区：
文献类型：
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作者：
Lobenhofer, EK;Bennett, L;Afshari, CA
类固醇激素雌激素可以刺激乳腺癌上皮细胞的有丝分裂反应。这种作用归因于ER的转录活性，ER是一种配体依赖性转录因子。然而，雌激素诱导增殖的确切分子机制尚未完全阐明。使用定制的cDNA微阵列包含许多基因参与细胞周期进程和DNA复制，我们研究了乳腺癌细胞系（MCF-7）的基因表达与促有丝分裂剂量的雌激素在血清中发现的混杂生长因子的情况下处理。在雌激素刺激后1、4、12、24、36和48小时监测基因表达变化，以便可以监测整个细胞周期进程中关键时刻的RNA水平。显著变化包括涉及转录、细胞信号传导和细胞周期检查点的基因的转录水平改变。在增加的细胞数量通过S期进展的时间点，也发现与DNA复制叉相关的大多数基因被诱导。在没有血清生长因子支持的情况下，雌激素与DNA复制叉基因的共表达表明雌激素诱导有丝分裂的分子机制中的一个重要的雌激素调节成分。
The steroid hormone estrogen can stimulate mitogenesis in hormone-responsive breast cancer epithelial cells. This action is attributed to the transcriptional activity of the ER, a ligand-dependent transcription factor. However, the exact molecular mechanism underlying estrogen-induced proliferation has yet to be completely elucidated. Using custom cDNA microarrays containing many genes implicated in cell cycle progression and DNA replication, we examined the gene expression of a hormone-responsive breast cancer cell line (MCF-7) treated with a mitogenic dose of estrogen in the absence of confounding growth factors found in serum. Gene expression changes were monitored 1, 4, 12, 24, 36, and 48 h after estrogen stimulation so that RNA levels at critical times throughout cell cycle progression could be monitored. Significant changes include the altered transcript levels of genes implicated in transcription, cellular signaling, and cell cycle checkpoints. At time points during which increased numbers of cells were progressing through S phase, a majority of the genes associated with the DNA replication fork were also found to be induced. The coexpression of DNA replication fork genes by estrogen without the support of serum growth factors indicates an important estrogen regulatory component of the molecular mechanism driving estrogen-induced mitogenesis.