Epidermal growth factor stimulates 3-hydroxy-3-methylglutaryl-coenzyme A reductase expression via the ErbB-2 pathway in human breast adenocarcinoma cells
Epidermal growth factor stimulates 3-hydroxy-3-methylglutaryl-coenzyme A reductase expression via the ErbB-2 pathway in human breast adenocarcinoma cells
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DOI：
10.1006/bbrc.1999.0945
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发表时间：
1999-07-14
影响因子：
3.1
通讯作者：
Le Gaillard, F
中科院分区：
文献类型：
--
作者：
Asslan, R;Pradines, A;Le Gaillard, F
HMG-CoA还原酶是细胞生长和分化所必需的类异戊二烯化合物生物合成的关键酶。最近在ErbB-2过表达细胞系SKBR-3中提出并描述了其酪氨酸激酶依赖性调节[Asslan等（1998）Biochem.J.330，241-246]。表皮生长因子（EGF）仅在ErbB-2表达细胞（SKBR-3和MCF-7）中增加HMG-CoA还原酶活性、蛋白质和mRNA水平，但在不表达ErbB-2的MDA-MB-468细胞中不增加，即使其EGF受体被有效磷酸化。Tyrphostin AG 879是ErbB-2酪氨酸激酶活性的特异性抑制剂，仅在表达ErbB-8的细胞中降低HMG-CoA还原酶活性。一个功能性的EGF受体似乎是必要的，因为它的抑制特定tyrphostin AG 1478废除了EGF的作用。磷脂酰肌醇3-激酶（PI 3-kinase）可能是信号通路中的关键酶，因为特异性抑制剂LY 294002被证明可以抑制HMG-CoA还原酶活性，并完全消除EGF对SKBR-3细胞的刺激。(C)北京：科学出版社.
HMG-CoA reductase is the key enzyme for the biosynthesis of isoprenoid compounds essential for cell growth and differentiation. Its tyrosine kinase-dependent modulation has recently been suggested and described in the ErbB-2 overexpressing cell line SKBR-3 [Asslan et al. (1998) Biochem. J. 330, 241-246]. Epidermal growth factor (EGF) increased the HMG-CoA reductase activity, protein, and mRNA levels only in ErbB-2-expressing cells (SKBR-3 and MCF-7) but not in MDA-MB-468 cells that do not express ErbB-2 even though their EGF receptor was efficiently phosphorylated. Tyrphostin AG 879, a specific inhibitor of ErbB-2 tyrosine kinase activity, decreased HMG-CoA reductase activity only in cells that expressed ErbB-8. A functional EGF receptor appeared to be necessary since its inhibition by the specific tyrphostin AG 1478 abolished the EGF effects. Phosphatidylinositol 3-kinase (PI3-kinase) might be a crucial enzyme in the signaling pathway since the specific inhibitor, LY 294002, was shown to inhibit HMG-CoA reductase activity and to completely abolish the stimulation by EGF in SKBR-3 cells. (C) 1999 Academic Press.