RECEPTOR TYROSINE KINASES AND DNA REPAIR

我们报告了DNA切除修复的一个成员的特征 在表达高水平胰岛素的细胞中增强的基因家族 受体或各种生长因子受体酪氨酸激酶。这个 利用逆转录技术克隆仓鼠ERCC-1部分基因 中国人细胞总RNA的聚合酶链式反应 表达人胰岛素受体的仓鼠卵巢细胞系(CHO/HIRc)。 它编码的蛋白质在氨基酸水平上的总体同源性是 与人和小鼠ERCC-1的同源性分别为91.3%和96%。CHO/HIRC细胞 和过表达功能活性的IGF-1受体和EGF的细胞 受体诱导ERCC-1基因表达水平升高 控制CHO/NEO细胞。增强型ERCC-1基因在人卵巢癌中的表达 CHO/HIRc细胞与对照CHO/neo细胞相比不能归因于 ERCC-1基因的细胞周期依赖性表达。此外，这一点 表达激酶缺陷的细胞中不存在ERCC-1基因的激活 胰岛素受体或带有取代的受体的突变形式 膜旁960位苯丙氨酸的酪氨酸 蛋白质的含量。ERCC-1基因表达水平与肺癌的发生、发展呈正相关 紫外线照射后细胞的表达和存活情况。最后，增强的 ERCC-1基因的表达与葡萄糖的利用无关，因为 所有细胞系的葡萄糖消耗率都是相同的。已被占用 总而言之，这些数据支持受体酪氨酸与 蛋白激酶活性与ERCC-1表达和功能的增强。

We report the characterization of a member of the DNA excision repair gene family that is enhanced in cells expressing high levels of insulin receptors or various growth factor receptor tyrosine kinases. The partial hamster ERCC-1 cDNA was cloned by reverse-transcription polymerase-chain reaction of total cellular RNA extracted from Chinese hamster ovary cell lines expressing human insulin receptors (CHO/HIRc). It encodes a protein whose overall homology at the amino acid level is 91.3% and 96% with human and murine ERCC-1, respectively. CHO/HIRc cells and cells overexpressing functionally active IGF-1 receptors and EGF receptors induced an increase of mRNA levels for ERCC-1 gene versus control CHO/neo cells. The enhanced expression of ERCC-1 mRNA in CHO/HIRc cells compared to control CHO/neo cells cannot be ascribed to cell cycle-dependent expression of the ERCC-1 gene. Moreover, this activation of ERCC-1 gene was absent in cells expressing kinase-deficient insulin receptors or a mutant form of the receptor with a substitution of tyrosine for phenylalanine at position 960 in the juxtamembrane region of the protein. There was a correlation between the level of ERCC-1 gene expression and cell survival after UV irradiation. Finally, the enhanced ERCC-1 gene expression was independent of glucose utilization since the rate of glucose consumption was identical in all cell lines. Taken together, these data support an association between receptor tyrosine kinase activity and enhancement of ERCC-1 expression and function.