Overexpression and activation of the insulin receptor enhances expression of ERCC-1 messenger ribonucleic acid in cultured cells.

In this study, a partial hamster complementary DNA encoding ERCC-1, a member of the DNA excision repair gene family, has been cloned. The nucleic acid and amino acid sequences were highly homologous to those of human and mouse ERCC-1. The hamster ERCC-1 gene was expressed as a 1.2-kilobase message in cultured Chinese hamster ovary cells. Northern (RNA) blot analysis revealed that overexpression of the insulin receptor or various growth factor receptor tyrosine kinases in Chinese hamster ovary cells increased ERCC-1 messenger RNA (mRNA) levels. This effect did not occur in cells overexpressing mutated insulin receptors that are known to have impaired kinase-related signaling. Increased ERCC-1 expression correlated with resistance to UV exposure. Fluorescent-activated cell sorter analysis of confluent cell populations indicated no differences in cell cycle distribution. Furthermore, no significant relationship was demonstrated between the relative expression of ERCC-1 mRNA and the rate of glucose utilization. Insulin enhanced the accumulation of ERCC-1 mRNA in serum-deprived cells expressing wild-type insulin receptors. The potential role for activation of the insulin receptor and related growth factor receptors in ERCC-1 gene expression and function remains to be defined.