Moscatello D K, Holgado-Madruga M, Godwin A K, Ramirez G, Gunn G, Zoltick P W, Biegel J A, Hayes R L, Wong A J
Department of Microbiology and Immunology, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Cancer Res. 1995 Dec 1;55(23):5536-9.
The epidermal growth factor receptor has received much interest as a target for various antineoplastic agents, but a complication is that many normal tissues also express this receptor. We have previously identified in human glial tumors an 801-bp in-frame deletion within the epidermal growth factor receptor gene that created a novel epitope at the junction. By using Western blot assays with a mutant-specific antibody as a rapid and sensitive means for detecting this alteration in primary human tumors, it was found that 57% (26 of 46) of high-grade and 86% (6 of 7) of low-grade glial tumors, but not normal brain, express this protein. This altered receptor was also present in 66% (4 of 6) of pediatric gliomas and 86% (6 of 7) of medulloblastomas, 78% (21 of 27) of breast carcinomas, and 73% (24 of 32) of ovarian carcinomas. The fact that this receptor is frequently found in tumors but not in normal tissue makes it an attractive candidate for various antitumor strategies.
表皮生长因子受体作为多种抗肿瘤药物的靶点备受关注，但一个复杂情况是许多正常组织也表达该受体。我们之前在人类胶质瘤中鉴定出表皮生长因子受体基因内一个801bp的框内缺失，该缺失在连接处产生了一个新的表位。通过使用针对突变体的特异性抗体进行蛋白质印迹分析，作为检测原发性人类肿瘤中这种改变的一种快速且灵敏的方法，发现57%（46例中的26例）的高级别胶质瘤和86%（7例中的6例）的低级别胶质瘤表达这种蛋白，而正常脑组织不表达。这种改变的受体也存在于66%（6例中的4例）的儿童胶质瘤、86%（7例中的6例）的髓母细胞瘤、78%（27例中的21例）的乳腺癌以及73%（32例中的24例）的卵巢癌中。这种受体在肿瘤中频繁出现而在正常组织中未发现这一事实，使其成为各种抗肿瘤策略的一个有吸引力的候选靶点。
