RECEPTOR TYROSINE KINASES AND DNA REPAIR

我们报告的一个成员的DNA切除修复的表征 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。 的 用逆转录法克隆了仓鼠ERCC-1的部分cDNA 中国人细胞总RNA的聚合酶链反应 表达人胰岛素受体（CHO/HIRc）的仓鼠卵巢细胞系。 它编码一种蛋白质，其在氨基酸水平上的总体同源性为 对人和鼠ERCC-1分别为91.3%和96%。 CHO/HIRc细胞 以及过度表达功能活性IGF-1受体和EGF的细胞 受体诱导ERCC-1基因mRNA水平增加， 对照CHO/neo细胞。 ERCC-1 mRNA表达增强， 与对照CHO/neo细胞相比，CHO/HIRc细胞不能归因于 ERCC-1基因的细胞周期依赖性表达。 而且这 ERCC-1基因的激活在表达激酶缺陷的细胞中不存在。 胰岛素受体或具有取代的受体的突变形式 在质膜区域的960位上，酪氨酸取代苯丙氨酸 蛋白质。 ERCC-1基因表达水平与乳腺癌的发生、发展密切相关， 表达和细胞存活。 最后，增强 ERCC-1基因表达与葡萄糖利用无关， 葡萄糖消耗速率在所有细胞系中相同。 采取 总之，这些数据支持受体酪氨酸 激酶活性和增强ERCC-1表达和功能。

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.