Dominance of ErbB-1 heterodimers in lung epithelial cells overexpressing ErbB-2. Both ErbB-1 and ErbB-2 contribute significantly to tumorigenicity.
Dominance of ErbB-1 heterodimers in lung epithelial cells overexpressing ErbB-2. Both ErbB-1 and ErbB-2 contribute significantly to tumorigenicity.
复制标题
ErbB-1 异二聚体在过度表达 ErbB-2 的肺上皮细胞中占主导地位。
DOI：
10.1165/ajrcmb.21.6.3784
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Gerwin,BI
中科院分区：
文献类型：
--
作者：
Fernandes,AM;Hamburger,AW;Gerwin,BI
This article examines differential expression and heterodimer formation of ErbB family members in tumorigenic and nontumorigenic human bronchial epithelial cells (HBECs). This cell system was developed previously as a model for lung adenocarcinoma by overexpression ofc-erbB-2in nontumorigenic, T antigen–immortalized HBECs. Earlier studies demonstrated that a tumorigenic clone from T antigen–immortalized nontumorigenic cells overexpressing ErbB-2 endogenously produced high levels of transforming growth factor (TGF)-α, and that reducing TGF-α by 93% eliminated tumorigenicity. In the present report, comparison of ErbB species between the tumorigenic cells (E6T) and their nontumorigenic derivatives (E6TA) demonstrated all four receptors in both cell types. However, in E6TA cells, ErbB-3 and -4 were present primarily in ErbB-1 heterodimers, suggesting that ErbB-1 is a preferred heterodimer partner within this cell system, expressing endogenous ErbB receptors and ligands and overexpressing ErbB-2. The ErbB-1/-2 species was present at high levels in E6T and absent in E6TA cells. Mitogen-activated protein kinase activity was elevated in E6T relative to E6TA. Elevated activity was eliminated by blocking surface expression of either ErbB-1 or ErbB-2. Endoplasmic reticulum trapping of ErbB-1 eliminated tumorigenicity, whereas ErbB-2 internalization was selected against during tumor formation. These data demonstrate the importance of TGF-α–mediated signaling through the ErbB-1/-2 heterodimer in development of the tumorigenic phenotype. This work further suggests that ErbB-3 and -4 species may also contribute to tumorigenic conversion and that their expression levels may be increased by signaling initiated by TGF-α.
