Epidermal growth factor receptor expression in. neurofibromatosis type 1-related tumors and NF1 animal models
Epidermal growth factor receptor expression in. neurofibromatosis type 1-related tumors and NF1 animal models
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DOI：
10.1172/jci7610
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发表时间：
2000-05-01
影响因子：
15.9
通讯作者：
Ratner, N
中科院分区：
文献类型：
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作者：
DeClue, JE;Heffelfinger, S;Ratner, N
我们已经发现EGF-R表达与神经纤维瘤病1型（NF 1）和这种疾病的动物模型的雪旺细胞衍生的肿瘤特征的发展有关。这是令人惊讶的，因为雪旺细胞通常缺乏EGF-R，并且对EGF以外的配体有反应。然而，免疫印迹、北方分析和免疫组织化学显示，3个来自NF 1患者的恶性外周神经鞘瘤（MPNST）细胞系中的每一个都表达EGFR，7个其他原发性MPNST中的7个、一个非NF 1 MPNST细胞系和9个良性神经纤维瘤中的每一个的S100（+）细胞也表达EGFR。此外，来自NF 1（-/-）小鼠胚胎的雪旺细胞的转化衍生物也表达EGF-R。所有表达EGF-R的细胞或细胞系都通过激活下游信号通路对EGF作出反应。因此，EGF-R的表达可能在NF 1肿瘤发生和雪旺细胞转化中起重要作用。与这一假设相一致，生长的NF 1 MPNST线和转化的NF 1（-/-）小鼠胚胎雪旺细胞在体外大大刺激EGF和拮抗EGF-R功能的药物可以被阻断。
We have found that EGF-R expression is associated with the development of the Schwann cell-derived rumors characteristic of neurofibromatosis type 1 (NF1) and in animal models of this disease. This is surprising, because Schwann cells normally lack EGF-R and respond to ligands other than EGF. Nevertheless, immunoblotting, Northern analysis, and immunohistochemistry revealed that each of 3 malignant peripheral nerve sheath tumor (MPNST) cell lines from NF1 patients expressed the EGFR, as did 7 of 7 other primary MPNSTs, a non-NF 1 MPNST cell line, and the S100(+) cells from each of 9 benign neurofibromas. Furthermore, transformed derivatives of Schwann cells from NF1 (-/-) mouse embryos also expressed the EGF-R. All of the cells or cell lines expressing EGF-R responded to EGF by activation of downstream signaling pathways. Thus, EGF-R expression may play an important role in NF1 tumorigenesis and Schwann cell transformation. Consistent with this hypothesis, growth of NF1 MPNST lines and the transformed NF1 (-/-) mouse embryo Schwann cells was greatly stimulated by EGF in vitro and could be blocked by agents that antagonize EGF-R function.