Differential effects of fibroblast growth factor on insulin receptor and muscle specific protein gene expression in BC3H-1 myocytes.
BC3H-1 mouse muscle cells in culture were employed to study the mechanisms which regulate insulin receptor gene expression during differentiation. When BC3H-1 myoblasts were plated in low serum media (1% fetal bovine serum), cell division ceased. Within 1 week cells had the morphological features of myocytes and expressed muscle specific proteins such as creatine phosphokinase and the nicotinic acetylcholine receptor. It is known that following incubation in low serum media, the steady state mRNA levels for the key muscle transcription factor, myogenin are increased. Exposure of BC3H-1 cells to a 20-base myogenin antisense oligomer blocked morphological differentiation, and resulted in nearly complete inhibition of the expression of the acetylcholine receptor but not the insulin receptor(IR). In order to study further the relationship between differentiation and IR gene expression, fibroblast growth factor (FGF), a known inhibitor of myogenic differentiation, was employed. FGF treatment inhibited the transcription of both myogenin and the acetylcholine receptor. However FGF did not inhibit the transcription of the IR. These studies indicate therefore that IR transcription increases during muscle cell differentiation, and suggest that during differentiation the control of IR gene expression differs from the control of muscle specific proteins.
Brunetti
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Department of Medicine, Mount Zion Hospital and Medical Center, San Francisco, California 94120.
Goldfine
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D000818:Animals; D001483:Base Sequence; D002038:Bungarotoxins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000235:genetics / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D007328:Insulin / Q000378:metabolism; D007457:Iodine Radioisotopes; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D009132:Muscles / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D018008:Myogenin; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D002038:Bungarotoxins; D007328:Insulin; D007457:Iodine Radioisotopes; D009124:Muscle Proteins; C503801:Myog protein, mouse; D018008:Myogenin; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors; D011972:Receptor, Insulin; D003402:Creatine Kinase