Hills D, Rowlinson-Busza G, Gullick W J
Imperial Cancer Research Fund Oncology Unit, Hammersmith Hospital, London, UK.
Int J Cancer. 1995 Nov 15;63(4):537-43. doi: 10.1002/ijc.2910630414.
A truncated epidermal growth factor receptor (EGFR) expressed from a rearranged and amplified EGFR gene is present at high frequency in gliomas. In this work we show that when this receptor is expressed in NIH3T3 fibroblasts it is partially activated and confers tumorigenicity to this cell line in vivo but no growth advantage in in vitro anchorage-independent growth assays. Because the mutation occurs in the extracellular domain of the receptor, it can be considered to represent a glioma-specific tumour marker. Here we demonstrate that 2 monoclonal antibodies, DH1.1 and DH8.3, raised to a synthetic peptide spanning the unique junctional sequence, can recognise the mutant receptor but not the normal receptor in both denatured and native states. Furthermore, radiolabelled antibody DH8.3 successfully targets tumours expressing this antigen in nude mice.
在胶质瘤中，由重排和扩增的表皮生长因子受体（EGFR）基因表达的截短型EGFR以高频率存在。在本研究中，我们发现，当该受体在NIH3T3成纤维细胞中表达时，它会被部分激活，并在体内赋予该细胞系致瘤性，但在体外非锚定依赖性生长试验中没有生长优势。由于该突变发生在受体的细胞外结构域，因此可以认为它代表一种胶质瘤特异性肿瘤标志物。在此，我们证明，针对跨越独特连接序列的合成肽产生的两种单克隆抗体DH1.1和DH8.3，在变性和天然状态下均能识别突变受体，但不能识别正常受体。此外，放射性标记的抗体DH8.3成功地靶向了裸鼠中表达该抗原的肿瘤。
