Blok L J, Grossmann M E, Perry J E, Tindall D J
Department of Urology Research, Mayo Clinic/Foundation, Rochester, Minnesota 55905, USA.
Mol Endocrinol. 1995 Nov;9(11):1610-20. doi: 10.1210/mend.9.11.8584037.
Using differential display polymerase chain reaction, early growth response gene alpha (EGR alpha) was first isolated as a 291-base pair 3'-cDNA clone, which was highly expressed in the androgen-independent prostate carcinoma cell lines PC3 and DU145, as compared with the androgen-responsive prostate carcinoma cell line LNCaP. Full length cloning of the EGR alpha coding region revealed that EGR alpha was a new member of an important subfamily of nuclear zinc finger transcription factors (others members e.g. Sp1, EGR-2, and Wilms' tumor gene). Moreover, it was observed that EGR alpha, as with most Sp1 subfamily members, was conserved between mammalian species ranging from human to rabbit. Two hormones important for prostate development and differentiation were found to be potent regulators of EGR alpha mRNA expression. Androgens were observed to induce a down-regulation of EGR alpha mRNA expression (70% in 72 h), while epidermal growth factor induced a rapid transient up-regulation (6-fold in 100 min). The up-regulation was controlled at the transcriptional level and effectively blocked by staurosporine (which suggests the involvement of the protein kinase C pathway). Functional analysis demonstrated that EGR alpha could bind to, and stimulate transcription from, a basic transcription element (BTE) consensus sequence on DNA (BTE is a transcription-modulating sequence in the promoter region of some cytochrome P450 family members). Furthermore, in stage-synchronized prostate cells, EGR alpha mRNA was highly expressed in the early G1 phase of the cell cycle, similar to c-fos mRNA expression. These results indicated that the zinc finger transcription factor EGR alpha seems to play a role in cell cycle regulation.
利用差异显示聚合酶链反应，早期生长反应基因α（EGRα）最初被分离为一个291个碱基对的3'-cDNA克隆，与雄激素反应性前列腺癌细胞系LNCaP相比，其在雄激素非依赖性前列腺癌细胞系PC3和DU145中高表达。EGRα编码区的全长克隆表明，EGRα是核锌指转录因子一个重要亚家族的新成员（其他成员如Sp1、EGR-2和威尔姆斯瘤基因）。此外，还观察到，与大多数Sp1亚家族成员一样，EGRα在从人到兔的哺乳动物物种之间是保守的。发现对前列腺发育和分化重要的两种激素是EGRα mRNA表达的有效调节因子。观察到雄激素可诱导EGRα mRNA表达下调（72小时内下调70%），而表皮生长因子可诱导快速短暂上调（100分钟内上调6倍）。这种上调在转录水平受到控制，并被星形孢菌素有效阻断（这表明蛋白激酶C途径参与其中）。功能分析表明，EGRα可以结合到DNA上的一个基本转录元件（BTE）共有序列并刺激其转录（BTE是一些细胞色素P450家族成员启动子区域中的转录调节序列）。此外，在阶段同步的前列腺细胞中，EGRα mRNA在细胞周期的早期G1期高表达，类似于c-fos mRNA的表达。这些结果表明，锌指转录因子EGRα似乎在细胞周期调节中发挥作用。
