Lobenhofer Edward K, Bennett Lee, Cable P LouAnn, Li Leping, Bushel Pierre R, Afshari Cynthia A
Gene Regulation Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Mol Endocrinol. 2002 Jun;16(6):1215-29. doi: 10.1210/mend.16.6.0858.
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.
类固醇激素雌激素可刺激激素反应性乳腺癌上皮细胞发生有丝分裂。这一作用归因于雌激素受体（ER）的转录活性，ER是一种依赖配体的转录因子。然而，雌激素诱导细胞增殖的确切分子机制尚未完全阐明。我们使用定制的cDNA微阵列，其中包含许多与细胞周期进程和DNA复制相关的基因，在不存在血清中所含混杂生长因子的情况下，检测了用有丝分裂剂量雌激素处理的激素反应性乳腺癌细胞系（MCF-7）的基因表达。在雌激素刺激后的1、4、12、24、36和48小时监测基因表达变化，以便能够监测整个细胞周期进程关键时间点的RNA水平。显著变化包括与转录、细胞信号传导和细胞周期检查点相关的基因转录水平改变。在更多细胞进入S期的时间点，还发现大多数与DNA复制叉相关的基因也被诱导。在没有血清生长因子支持的情况下，雌激素使DNA复制叉基因共表达，这表明雌激素在驱动雌激素诱导的有丝分裂分子机制中具有重要的调控作用。
