title: 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.affiliation: Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland 20892, USA. jd99f@nih.gov
authors.forename: J E
authors.initials: JE
authors.lastname: DeClue
authors.forename: S
authors.initials: S
authors.lastname: Heffelfinger
authors.forename: G
authors.initials: G
authors.lastname: Benvenuto
authors.forename: B
authors.initials: B
authors.lastname: Ling
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Rui
authors.forename: W C
authors.initials: WC
authors.lastname: Vass
authors.forename: D
authors.initials: D
authors.lastname: Viskochil
authors.forename: N
authors.initials: N
authors.lastname: Ratner
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D009442:Neurilemmoma; D009456:Neurofibromatosis 1 / Q000378:metabolism*; D025542:Neurofibromin 1; D011506:Proteins / Q000235:genetics*; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D025542:Neurofibromin 1; D011506:Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors