The effects of prostaglandin E2, parathyroid hormone, and epidermal growth factor on mitogenesis, signaling, and primary response genes in UMR 106-01 osteoblast-like cells.
The effects of prostaglandin E2, parathyroid hormone, and epidermal growth factor on mitogenesis, signaling, and primary response genes in UMR 106-01 osteoblast-like cells.
复制标题
DOI：
10.1210/endo.131.5.1330491
复制
发表时间：
1992-11
期刊：
影响因子：
4.8
通讯作者：
M. Fang;D. Kujubu;T. Hahn
中科院分区：
文献类型：
--
作者：
M. Fang;D. Kujubu;T. Hahn
前列腺素E2(PGE2)、甲状旁腺素(PTH)和表皮生长因子(EGF)是成骨细胞增殖的有效调节因子。在具有成骨样特征的UMR 106-01大鼠骨肉瘤细胞中，PGE2和PTH抑制，而EGF刺激有丝分裂生成。前列腺素E_2和甲状旁腺素均可增加细胞内cAMP水平、细胞内钙离子和肌醇磷酸转换率。在各种类型的细胞中，EGF部分通过激活受体蛋白酪氨酸激酶和其他蛋白激酶，如蛋白激酶C，来调节其效应。PGE2、PTH和EGF对成骨细胞增殖的核调控机制尚不清楚。因此，我们研究了这些药物对有丝分裂、第二信使生成和初级反应基因的影响，这些基因可能将第二信使激活与随后的基因表达变化联系起来。用2微米PGE2、10 nM甲状旁腺素或10 ng/mlEGF处理UMR 106-01细胞3h后，Northern印迹分析显示三种药物均可诱导c-fos和c-jun基因的表达。相反，只有EGF刺激细胞增殖并诱导Egr-1mRNA表达。此外，与PGE2和PTH不同，EGF不会增加细胞内cAMP水平。50 ng/ml佛波酯或40 ng/mlforskolin均可诱导c-fos基因的表达，而Egr-1mRNA的表达可被佛波醇乙酸酯刺激，但不能被福司可林诱导。因此，在UMR 106-01成骨样细胞中，EGF的信号转导不同于PGE2和PTH，因为EGF不刺激蛋白激酶A第二信使系统，而引起Egr-1的激活，Egr-1是可能在EGF的有丝分裂作用中发挥作用的主要反应基因。
Prostaglandin E2 (PGE2), PTH, and epidermal growth factor (EGF) are potent regulators of osteoblast proliferation. In UMR 106-01 rat osteosarcoma cells with osteoblast-like features, PGE2 and PTH inhibit, while EGF stimulates, mitogenesis. Both PGE2 and PTH increase intracellular cAMP levels, cytosolic calcium, and inositol phosphate turnover. In a variety of cell types, EGF mediates its effects in part via activation of receptor protein-tyrosine kinase and other protein kinases, such as protein kinase-C. The nuclear mechanisms of PGE2, PTH, and EGF regulation of osteoblast proliferation are unknown. Accordingly, we have examined the effects of these agents on mitogenesis, second messenger generation, and primary response genes, which may link second messenger activation to subsequent alterations in gene expression. Northern blot analysis of mRNA from UMR 106-01 cells treated for 3 h with 2 microM PGE2, 10 nM PTH, or 10 ng/ml EGF in the presence of cycloheximide demonstrated that all three agents induced the expression of c-fos and c-jun mRNA. In contrast, only EGF stimulated cellular proliferation and induced Egr-1 mRNA. Also, unlike PGE2 and PTH, EGF did not increase intracellular cAMP levels. c-fos mRNA was induced by treatment with 50 ng/ml tetradecanoyl phorbol acetate or by 40 ng/ml forskolin, while induction of Egr-1 mRNA was stimulated by treatment with tetradecanoyl phorbol acetate, but not forskolin. Thus, EGF signal transduction differs from that of PGE2 and PTH in UMR 106-01 osteoblast-like cells, in that EGF does not stimulate the protein kinase-A second messenger system, but causes activation of Egr-1, a primary response gene that may play a role in the mitogenic effect of EGF.