Identification of a specific pattern of "immediate-early" gene activation induced by estrogen during mitogenic stimulation of rat uterine cells.
Identification of a specific pattern of "immediate-early" gene activation induced by estrogen during mitogenic stimulation of rat uterine cells.
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鉴定雌激素在大鼠子宫细胞有丝分裂刺激期间诱导的“立即早期”基因激活的特定模式。
DOI：
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发表时间：
1993
期刊：
影响因子：
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通讯作者：
Alessandro Weisz
中科院分区：
文献类型：
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作者：
L. Cicatiello;Sica;Francesco Bresciani;Alessandro Weisz
雌激素是某些靶组织的有效有丝分裂原，它们通过诱导周期中静止细胞的募集和促进细胞周期进展来刺激细胞生长。为了确定这些类固醇激素促有丝分裂作用的分子基础，在体内雌激素刺激大鼠子宫细胞的早期阶段监测“立即早期”基因表达模式。核连续转录和/或 Northern blot RNA 分析表明，成人治疗后 30-120 分钟内，c-jun、junB、jun-D、c-fos、TIS 1（也称为 NGFI-B 或 nur/77）和 TIS 8（zif-268、krox24、egr-1 或 NGFI-A）基因均在子宫中瞬时激活（高达 20 倍）卵巢切除大鼠 使用促有丝分裂剂量的 17b-雌二醇。相反，JE 基因 mRNA 在雌激素刺激的子宫细胞中逐渐积累，而 TIS 11 和 21 基因仅对激素有轻微反应（小于两倍诱导），并且在雌激素治疗之前或之后，在大鼠子宫中检测不到 fos B、fra-1、fra-2、krox20 (egr-2)、TIS 7 和 10、KC 和 c-rel mRNA。放线菌酮存在下的刺激表明，只有 c-jun、jun-D、c-fos 和 JE 基因激活是大鼠子宫细胞对该激素的主要反应。这些发现确立了雌激素的直接促有丝分裂作用，并首次确定了这些类固醇激素在刺激靶细胞增殖过程中激活的特定遗传程序。此外，由于大多数激活的基因编码转录因子，这些结果使我们能够想象激素传递的有丝分裂信号如何通过雌激素反应基因的产物在靶细胞内被精心设计和放大，从而导致生长依赖性基因调控、细胞周期进程以及最终的细胞分裂的级联反应。
Estrogen hormones are potent mitogens for certain target tissues, where they stimulate cell growth by inducing recruitment of quiescent cells in cycle and by fostering cell cycle progression. To define the molecular bases of the mitogenic action of these steroid hormones, the pattern of "immediate-early" gene expression was monitored during the early phases of estrogen stimulation of rat uterine cells in vivo. Nuclear run-on transcription and/or Northern blot RNA analysis indicate that c-jun, junB, jun-D, c-fos, TIS 1 (also called NGFI-B or nur/77) and TIS 8 (zif-268, krox24, egr-1, or NGFI-A) genes are all transiently activated in the uterus (up to 20-fold) within 30-120 min after treatment of adult ovariectomized rats with a mitogenic dose of 17b-estradiol. Conversely, JE gene mRNA accumulates progressively in estrogen-stimulated uterine cells, whereas TIS 11 and 21 genes are only slightly responsive to the hormone (less than twofold induction) and fos B,fra-1,fra-2,krox20 (egr-2), TIS 7 and 10, KC, and c-rel mRNAs are undetectable in rat uterus either before or after estrogen treatment. Stimulation in the presence of cycloheximide shows that only c-jun, jun-D, c-fos, and JE gene activations are primary responses to the hormone in rat uterine cells. These findings establish the direct mitogenic role of estrogen and identify for the first time a specific genetic program activated by these steroid hormones during stimulation of target cell proliferation. Furthermore, since most of the activated genes encode for transcription factors, these results enable us to envision how the mitogenic signal transmitted by the hormone can be elaborated and amplified within target cells by the products of estrogen-responsive genes, leading to a cascade of growth-dependent gene regulation, cell cycle progression, and, ultimately, cell division.