Epidermal growth factor receptor expression in neurofibromatosis type 1–related tumors and NF1 animal models
Autor: | Giovanna Benvenuto, Nancy Ratner, Bo Ling, William C. Vass, David Viskochil, Shaowei Li, Sue C. Heffelfinger, Jeffrey E. DeClue, Wen Rui |
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Rok vydání: | 2000 |
Předmět: |
congenital
hereditary and neonatal diseases and abnormalities medicine.medical_specialty Neurofibromatosis 1 Schwann cell Malignant peripheral nerve sheath tumor Biology medicine.disease_cause Article Mice Epidermal growth factor Internal medicine Tumor Cells Cultured medicine Animals Humans Epidermal growth factor receptor Neurofibromatosis Neurofibromin 1 Epidermal Growth Factor Proteins General Medicine medicine.disease Mice Mutant Strains Rats ErbB Receptors Cell Transformation Neoplastic medicine.anatomical_structure Endocrinology Cell culture biology.protein Cancer research Carcinogenesis Neurilemmoma hormones hormone substitutes and hormone antagonists |
Zdroj: | Journal of Clinical Investigation. 105:1233-1241 |
ISSN: | 0021-9738 |
Popis: | 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. |
Databáze: | OpenAIRE |
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