Overexpression of ErbB2 impairs ligand‐dependent downregulation of epidermal growth factor receptors via a post‐transcriptional mechanism
Overexpression of ErbB2 impairs ligand‐dependent downregulation of epidermal growth factor receptors via a post‐transcriptional mechanism
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ErbB2 的过度表达通过转录后机制损害表皮生长因子受体的配体依赖性下调
DOI：
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发表时间：
1999
影响因子：
4
通讯作者：
R. Epstein
中科院分区：
文献类型：
--
作者：
G. Huang;A. Chantry;R. Epstein
ErbB2发挥致癌作用的机制尚不清楚。在这篇文章中，我们证明了ErbB2的共同表达减缓了NIH3T3转染体中配体依赖性生长因子受体的下调。在表皮生长因子受体(EGFR)转基因细胞中，细胞生长的配体依赖性和MAP激酶信号被保留，而在表达ErbB2的细胞中则被取消，后者是结构性生长和信号传递的。与这一现象相关的是，我们注意到表达ErbB2的细胞含有过量的过度磷酸化的EGFR。然而，EGFR过表达不包含增加的ErbB2水平，倾向于排除由受体处理饱和引起的转染伪影。EGFR转染体经EGF处理后，EGFR下调的速度比ErbB2转染组更快，但Northern印迹分析显示ErbB2转染体的基本EGFR基因表达减少。我们的结论是ErbB2的表达通过转录后机制损害了EGFR的下调，并认为ErbB2的过表达可能通过延缓连接的异二聚体的降解而使肿瘤细胞对异源生长因子的促有丝分裂作用敏感。J.细胞。生物化学。74：23-30,1999.©1999 Wiley-Liss，Inc.
The mechanism by which ErbB2 exerts its oncogenic effect is poorly defined. In this article we show that ErbB2 co‐expression slows ligand‐dependent growth factor receptor downregulation in NIH 3T3 transfectants. Ligand dependence of cell growth and MAP kinase signaling are retained in epidermal growth factor receptor (EGFR) transfectants but are abolished in ErbB2‐expressing cells, which grow and signal constitutively. In association with this phenomenon, we have noticed that ErbB2‐expressing cells contain increased amounts of EGFR, which is hyperphosphorylated. EGFR overexpressors do not contain increased levels of ErbB2, however, tending to exclude a transfection artifact caused by saturation of receptor processing. EGF treatment of EGFR transfectants results in more rapid EGFR downregulation than occurs in ErbB2 transfectants, but Northern blot analysis demonstrates reduced basal EGFR gene expression in ErbB2 transfectants. We conclude that ErbB2 expression impairs EGFR downregulation via a post‐transcriptional mechanism and propose that ErbB2 overexpression may sensitize tumor cells to the mitogenic effects of heterologous growth factors by retarding degradation of liganded heterodimers. J. Cell. Biochem. 74:23–30, 1999. © 1999 Wiley‐Liss, Inc.
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影响因子：
56.9
作者：
WELLS, A;WELSH, JB;ROSENFELD, MG
通讯作者：
ROSENFELD, MG
DOI：
10.1073/pnas.92.19.8719
发表时间：
1995-09-12
影响因子：
11.1
作者：
NESTEROV, A;WILEY, HS;GILL, GN
通讯作者：
GILL, GN
影响因子：
56.9
作者：
SLAMON, DJ;CLARK, GM;MCGUIRE, WL
通讯作者：
MCGUIRE, WL
人鳞状癌细胞中自分泌转化生长因子α途径的激活。
影响因子：
11.2
作者：
Reiss,M;Stash,EB;Vellucci,VF;Zhou,ZL
通讯作者：
Zhou,ZL
DOI：
--
发表时间：
1995
期刊：
Oncogene.
影响因子：
--
作者：
Galcheva-Gargova,Z;Theroux,SJ;Davis,RJ
通讯作者：
Davis,RJ