Epidermal growth factor regulation of equine glycoprotein hormone alpha subunit expression in trophoblast cells.
Epidermal growth factor regulation of equine glycoprotein hormone alpha subunit expression in trophoblast cells.
复制标题
表皮生长因子对滋养层细胞中马糖蛋白激素α亚基表达的调节。
DOI：
10.1095/biolreprod65.1.197
复制
发表时间：
2001
影响因子：
3.6
通讯作者：
Wolfe,MW
中科院分区：
文献类型：
--
作者：
Thway,TM;Wolfe,MW
灵长类动物和马科动物是已知表达胎盘糖蛋白激素绒毛膜促性腺激素（CG）的唯一物种，CG是一种由α亚基连接至胎盘特异性β亚基的异二聚体糖蛋白。马糖蛋白α亚基基因表达诱导的调控机制尚未确定。已知表皮生长因子（EGF）受体抑制改变许多不同细胞功能（细胞增殖、分化、激素分泌和基因调节）的信号。在本研究中，我们研究了马α亚基基因的调控EGF在滋养细胞。我们发现马α亚基启动子5′侧翼序列的2800碱基对足以在人绒毛膜癌细胞中进行基础表达。表皮生长因子和佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA），蛋白激酶C（PKC）的激活剂，增加马α亚基启动子的转录活性（−2800/+21）。这些反应被阻断预处理与bisindolylmaleimide-I，PKC的抑制剂，这表明参与EGF的下游这一途径。此外，细胞外信号调节激酶（ERK）通路抑制剂PD 98059可完全阻断PMA对马α启动子的激活，表明PKC通路下游参与了丝裂原活化蛋白激酶（MAPK）级联反应。总之，EGF/PKC/MAPK途径通过滋养层中不同的调节区域（-2300至-1900）调节马糖蛋白α亚基基因表达，而基础表达的必需元件似乎存在于启动子的-2800至-1900区域内。
Primates and equids are the only species known to express the placental glycoprotein hormone, chorionic gonadotropin (CG), a heterodimeric glycoprotein composed of an α subunit linked to a hormone-specific β subunit. The regulatory mechanisms involved in the induction of equine glycoprotein α subunit gene expression have not been identified. Epidermal growth factor (EGF) receptor is known to transduce signals that alter a number of different cellular functions (cell proliferation, differentiation, hormone secretion, and gene regulation). In the present study, we investigated the regulation of the equine α subunit gene by EGF in trophoblasts. We found that 2800 base pairs of 5′ flanking sequence from the equine α subunit promoter is sufficient for basal expression in human choriocarcinoma cells. Epidermal growth factor and phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), increased transcriptional activity of the equine α subunit promoter (−2800/+21). These responses were blocked by pretreatment with bisindolylmaleimide-I, an inhibitor of PKC, suggesting an involvement of this pathway downstream of EGF. In addition, PD98059, an inhibitor of the extracellular signal-regulated kinase (ERK) pathway, completely blocked activation of the equine α promoter by PMA, suggesting that mitogen-activated protein kinase (MAPK) cascade was involved downstream of the PKC pathway. In conclusion, the EGF/PKC/MAPK pathway regulates equine glycoprotein α subunit gene expression through a distinct regulatory region (−2300 to −1900) in trophoblasts, while essential elements for basal expression appear to exist within the −2800 to −1900 region of the promoter.