INDUCTION OF C-FOS AND C-MYC MESSENGER-RNA EXPRESSION BY IMMUNOGLOBULIN-G FROM PATIENTS WITH GRAVES-DISEASE IN THYROTROPIN-DEPENDENT RAT-THYROID CELL-LINE (FRTL5)

The present study was conducted to evaluate effects of autoantibodies in patients with Graves' disease on induction of c-fos and c-myc mRNA expression in rat thyroid cell line (FRTL5). IgG fractions were isolated from 11 patients with Graves' disease, and six healthy subjects, with protein A-Sepharose. FRTL5 cells which had been grown to subconfluency and deprived of TSH for a week were exposed to the IgG for an hour. Expression of c-fos and c-myc mRNAs was examined by the Northern blot method using nick-translated v-fos and c-myc probes. C-fos and c-myc transcripts were induced by IgGs from two patients with Graves' disease, which displayed much higher activities in assays for TSH binding inhibitor immunoglobulins, thyroid stimulating antibodies and thyroid growth-stimulating immunoglobulins, assessed by measuring inhibition of I-125-TSH binding to the TSH-receptor, cAMP production and H-3-thymidine incorporation in FRTL5 cells, respectively, compared with those in the remaining patients. The induction of c-fos and c-myc mRNAs by IgG from a patient with Graves' disease was suppressed by preincubation with IgGs from two patients with primary myxoedema who were known to have a blocking type TSH-receptor antibody. These data suggest that the binding of the antibodies to the TSH-receptor followed by cAMP production is related to the induction of c-fos and c-myc mRNAs and, thus, to the growth of FRTL5 cells. To our knowledge, this is the first report demonstrating that autoantibodies induce proto-oncogene mRNA expression.