Epidermal growth factor receptor expression in neurofibromatosis type 1–related tumors and NF1 animal models
Jeffrey E. DeClue, Sue Heffelfinger, Giovanna Benvenuto, Bo Ling, Shaowei Li, Wen Rui, William C. Vass, David Viskochil, Nancy Ratner
Jeffrey E. DeClue, Sue Heffelfinger, Giovanna Benvenuto, Bo Ling, Shaowei Li, Wen Rui, William C. Vass, David Viskochil, Nancy Ratner
View: Text | PDF
Article

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

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

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Transformed derivatives of NF1 (–/–) mouse embryo–derived Schwann cells ...
Transformed derivatives of NF1 (–/–) mouse embryo–derived Schwann cells have elevated basal MAP kinase activity and respond to EGF. (a) Mouse Schwann cells were isolated from day 12.5 embryos with wild-type NF1 (+/+) or targeted disruption of one NF1 allele (+/–), or both alleles (–/–), and compared with transformed derivatives of (–/–) (TXF). The cells were serum starved for 24 hours, then left untreated or stimulated with GGF, as indicated. Cells were lysed and MAP kinase activity was determined as for Figure 1. Results are the mean of two experiments carried out in duplicate, with error bars shown. Results were normalized to the level of activity present in serum-starved wild-type (+/+) cells (1.0). (b) Schwann cells from (–/–) embryos and TXF were treated and assayed as above, except additional samples were prepared after stimulation with 50 ng/mL EGF for 5 minutes. Results are the mean of two experiments carried out in duplicate, with error bars shown. Results were normalized to the level of activity present in serum-starved homozygous null (–/–) cells (1.0).