MODULATION OF HEPATOCYTE GROWTH-FACTOR GENE-EXPRESSION BY ESTROGEN IN MOUSE OVARY
MODULATION OF HEPATOCYTE GROWTH-FACTOR GENE-EXPRESSION BY ESTROGEN IN MOUSE OVARY
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DOI：
10.1016/0303-7207(94)90120-1
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发表时间：
1994-09-01
影响因子：
4.1
通讯作者：
ZARNEGAR, R
中科院分区：
文献类型：
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作者：
LIU, YH;LIN, L;ZARNEGAR, R
肝细胞生长因子（HGF）在正常条件下和响应于各种刺激如组织损伤在多种组织和细胞类型中表达。在本研究中，我们证明了HGF基因的转录是由雌激素刺激小鼠卵巢。单次注射17 β-雌二醇导致小鼠HGF mRNA水平的急剧和短暂升高。序列分析发现，小鼠HGF基因5 ′侧翼区的-872和第一内含子的+511处分别存在两个推定的雌激素反应元件（ERE）。为了检测这些ERE元件是否与雌激素诱导HGF基因表达有关，将含有HGF基因5 '侧翼序列可变区和氯霉素乙酰转移酶（CAT）基因编码区的嵌合质粒瞬时转染人子宫内膜癌RL 95-2细胞和小鼠成纤维细胞NIH 3 T3细胞，以评估激素反应性。转染结果表明，小鼠HGF基因的ERE元件可以将雌激素作用赋予同源或异源启动子。从转染雌激素受体表达载体的RL 95 -2细胞或从小鼠肝脏中提取的核蛋白提取物在体外特异性地结合到ERE元件，如带移分析所示。因此，我们的研究结果表明，HGF基因的转录调节雌激素在小鼠卵巢中，这种调节是通过直接相互作用的雌激素受体复合物与顺式作用的ERE元件中确定的小鼠HGF基因介导的。
Hepatocyte growth factor (HGF) is expressed in a variety of tissues and cell types under normal conditions and in response to various stimuli such as tissue injury. In the present study, we demonstrate that the transcription of the HGF gene is stimulated by estrogen in mouse ovary. A single injection of 17 beta-estradiol results in a dramatic and transient elevation of the levels of mouse HGF mRNA. Sequence analysis has found that two putative estrogen responsive elements (ERE) reside at -872 in the 5'-flanking region and at +511 in the first intron, respectively, of the mouse HGF gene. To test whether these ERE elements are responsible for estrogen induction of HGF gene expression,chimeric plasmids containing variable regions of the 5'-flanking sequence of HGF gene and the coding region for chloramphenicol acetyltransferase (CAT) gene were transiently transfected into both human endometrial carcinoma RL 95-2 cells and mouse fibroblast NIH 3T3 cells to assess hormone responsiveness. Transfection results indicate that the ERE elements of the mouse HGF gene can confer estrogen action to either homologous or heterologous promoters. Nuclear protein extracts either from RL95-2 cells transfected with the estrogen receptor expression vector or from mouse liver bound in vitro to ERE elements specifically, as shown by band shift assay. Therefore, our results demonstrate that the HGF gene is transcriptionally regulated by estrogen in mouse ovary; and such regulation is mediated via a direct interaction of the estrogen receptor complex with cis-acting ERE elements identified in the mouse HGF gene.