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 nu cleic 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 recepto r or various growth factor receptor tyrosine kinases in Chinese hamste r ovary cells increased ERCC-1 messenger RNA (mRNA) levels. This effec t 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-act ivated cell sorter analysis of confluent cell populations indicated no differences in cell cycle distribution. Furthermore, no significant r elationship was demonstrated between the relative expression of ERCC-1 mRNA and the rate of glucose utilization. Insulin enhanced the accumu lation of ERCC-1 mRNA in serum-deprived cells expressing wild-type ins ulin receptors. The potential role for activation of the insulin recep tor and related growth factor receptors in ERCC-1 gene expression and function remains to be defined.