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.
View: Text | PDF
Article Article has an altmetric score of 3

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 4

Options: View larger image (or click on image) Download as PowerPoint
Growth of NF1 patient MPNST lines is EGF dependent and is inhibited by E...
Growth of NF1 patient MPNST lines is EGF dependent and is inhibited by EGF-R antagonists. (a) MPNST line 88-14 was plated at 2 × 104 per 35-mm well. The next day (day 1) cells were switched to medium without (–EGF) or with 10 ng/mL EGF (+EGF), and on day 2 cells were switched to medium containing 10 ng/mL EGF and 3% PBS (Veh1); 0.1% DMSO (Veh2); 3 μg/mL mAb 225 in PBS (3% vol/vol; mAb); 40 μM farnesyltransferase inhibitor B581 in water; 10 μM tyrphostin A-25 in DMSO; or 400 nM tyrphostin AG-1478, also in DMSO. Cells were re-fed with medium containing fresh inhibitor and counted in duplicate every 2 days, beginning at day 2. (b) Growth of MPNST 88-14 line in soft agar. Cells were plated at 105/mL in a 0.4% (wt/vol) agar suspension with 7% FBS with or without 100 ng/mL EGF, as indicated; mAb 225 was included at 5 μg/mL and AG-1478 at 400 nM. Cells were photographed after 4 weeks. × 25. (c and d) Growth of 88-14 (c) and 90-8 (d) in 2% serum is inhibited by EGF-R antagonists. Cells were plated as in a, and switched on day 1 to medium containing 2% FBS (CON) or 2% serum plus 0.1% DMSO (Veh); 3 μg/mL mAb 225 (mAb); 10 μM tyrphostin A-25; or 400 nM tyrphostin AG-1478. Thereafter, cells were re-fed with medium containing fresh inhibitor every 2 days, and duplicate wells of cells were counted every three days.