Induction of c-fos and c-myc mRNA expression by immunoglobulin G from patients with Graves' disease in thyrotrophin-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 125I-TSH binding to the TSH-receptor, cAMP production and 3H-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.
Hatabu
H
H
Department of Radiology and Nuclear Medicine, Faculty of Medicine, Kyoto University, Japan.
Kasagi
K
K
Iida
Y
Y
Nosaka
T
T
Misaki
T
T
Hidaka
A
A
Tokuda
Y
Y
Endo
K
K
Mori
T
T
Lee
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000235:genetics*; D015152:Blotting, Northern; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000276:immunology*; D006111:Graves Disease / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism; D013997:Time Factors
D001323:Autoantibodies; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D013972:Thyrotropin