Humphrey P A, Gangarosa L M, Wong A J, Archer G E, Lund-Johansen M, Bjerkvig R, Laerum O D, Friedman H S, Bigner D D
Departments of Pathology, Duke University Medical Center, Durham, NC 27710.
Biochem Biophys Res Commun. 1991 Aug 15;178(3):1413-20. doi: 10.1016/0006-291x(91)91051-d.
Malignant human glioma D-298 MG amplifies a rearranged epidermal growth factor receptor (EGFR) gene (c-erbB proto-oncogene), resulting in an in-frame deletion of 83 amino acids in domain IV of the extracellular domain of the EGFR. EGF and transforming growth factor-a (TGF-a) bound to the mutant EGFR with high affinity and enhanced the intrinsic mutant EGFR kinase activity. The mutant EGFR was capable of transducing EGF-stimulated glioma cell proliferation and invasiveness in an in vitro three-dimensional spheroid model. The deletion-mutant EGFR in D-298 MG is capable of being activated by growth factor; this suggests that overexpression of this mutant EGFR protein rather than structural alteration may be the more significant biologic event.
恶性人类胶质瘤D - 298 MG扩增了一个重排的表皮生长因子受体（EGFR）基因（c - erbB原癌基因），导致EGFR胞外结构域IV区有83个氨基酸的读框内缺失。表皮生长因子（EGF）和转化生长因子 - α（TGF - α）以高亲和力结合到突变型EGFR上，并增强了突变型EGFR的内在激酶活性。在体外三维球体模型中，突变型EGFR能够转导EGF刺激的胶质瘤细胞增殖和侵袭。D - 298 MG中的缺失突变型EGFR能够被生长因子激活；这表明该突变型EGFR蛋白的过表达而非结构改变可能是更重要的生物学事件。
