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

We have found that EGF-R expression is associated with the development of t he Schwann cell-derived rumors characteristic of neurofibromatosis type 1 ( NF1) and in animal models of this disease. This is surprising, because Schw ann cells normally lack EGF-R and respond to ligands other than EGF. Nevert heless, immunoblotting, Northern analysis, and immunohistochemistry reveale d 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 neu rofibromas. Furthermore, transformed derivatives of Schwann cells from NF1 (-/-) mouse embryos also expressed the EGF-R. All of the cells or cell line s expressing EGF-R responded to EGF by activation of downstream signaling p athways. Thus, EGF-R expression may play an important role in NF1 tumorigen esis and Schwann cell transformation. Consistent with this hypothesis, grow th of NF1 MPNST lines and the transformed NF1 (-/-) mouse embryo Schwann ce lls was greatly stimulated by EGF in vitro and could be blocked by agents t hat antagonize EGF-R function.