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Epidermal growth factor receptor expression in neurofibromatosis type 1–related tumors and NF1 animal models
Jeffrey E. DeClue, … , David Viskochil, Nancy Ratner
Jeffrey E. DeClue, … , David Viskochil, Nancy Ratner
Published May 1, 2000
Citation Information: J Clin Invest. 2000;105(9):1233-1241. https://doi.org/10.1172/JCI7610.
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Article

Epidermal growth factor receptor expression in neurofibromatosis type 1–related tumors and NF1 animal models

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Abstract

We have found that EGF-R expression is associated with the development of the Schwann cell–derived tumors 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 EGF-R, as did 7 of 7 other primary MPNSTs, a non-NF1 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.

Authors

Jeffrey E. DeClue, Sue Heffelfinger, Giovanna Benvenuto, Bo Ling, Shaowei Li, Wen Rui, William C. Vass, David Viskochil, Nancy Ratner

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