Han Y, Caday C G, Nanda A, Cavenee W K, Huang H J
Department of Neurosurgery, Louisiana State University Medical Center, Shreveport 71130, USA.
Cancer Res. 1996 Sep 1;56(17):3859-61.
The effects of a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, tyrphostin AG 1478, were tested on three related human glioma cell lines: U87MG, which expressed endogenous wild-type (wt) EGFR, and two retrovirally infected U87MG cell populations which over-expressed either wt (U87MG.wtEGFR) or truncated EGFR (U87MG. delta EGFR). Although AG 1478 inhibited cell growth, DNA synthesis, EGFR tyrosine kinase activity, and receptor autophosphorylation of each cell line in a dose-dependent manner, it was significantly more potent in U87MG. delta EGFR cells than in the other two cell lines. The increased inhibitory response of U87MG. delta EGFR cells was due to a greater sensitivity of the constitutively autophosphorylated Mr 140,000 and 155,000 delta EGFR species to AG 1478. These results suggest that AG 1478 is a relatively specific inhibitor of the delta EGFR, and this finding may have important therapeutic implications since the delta EGFR occurs frequently in glioblastomas and in breast, lung, and ovarian cancers.
一种新型表皮生长因子受体（EGFR）酪氨酸激酶抑制剂 tyrphostin AG 1478，在三种相关的人胶质瘤细胞系上进行了测试：表达内源性野生型（wt）EGFR的U87MG，以及两个逆转录病毒感染的U87MG细胞群体，它们分别过表达wt（U87MG.wtEGFR）或截短的EGFR（U87MG.δEGFR）。尽管AG 1478以剂量依赖性方式抑制了每个细胞系的细胞生长、DNA合成、EGFR酪氨酸激酶活性和受体自身磷酸化，但它在U87MG.δEGFR细胞中的效力明显高于其他两个细胞系。U87MG.δEGFR细胞抑制反应的增强是由于组成性自身磷酸化的分子量为140,000和155,000的δEGFR对AG 1478的敏感性更高。这些结果表明AG 1478是δEGFR的相对特异性抑制剂，这一发现可能具有重要的治疗意义，因为δEGFR在胶质母细胞瘤以及乳腺癌、肺癌和卵巢癌中频繁出现。
