Overexpression of c-erbA proto-oncogene enhances myogenic differentiation.
Triiodothyronine (T3) positively regulates both the expression of the MyoD gene, a key myogenic regulator, and C2 muscle cell differentiation. To directly examine the role of its nuclear receptors in the control of myogenesis, we introduced a c-erbA expression vector into C2 muscle cells by transient or stable transfection. Our results show that c-erbA can play a potent role in the triggering of muscle terminal differentiation since its overexpression leads to: (1) a complete abrogation of the activity of the myogenesis inhibitor AP-1 (fos/jun) transcription factor; (2) an enhanced induction of MyoD expression upon T3 treatment; (3) the acquisition by T3 of the ability to trigger both growth arrest and terminal differentiation in the presence of large amounts of serum mitogens, a property that is otherwise specific to retinoic acid (RA). Thus, c-erbA is one of the two protooncogenes (with c-ski) that acts as positive regulator of muscle differentiation. Furthermore, the fact that c-erbA overexpression allows T3 to largely mimic the RA effects indicates that their biological differences in the modulation of myogenic program primarily rely on the differential expression of their receptors in C2 muscle cells rather than on an intrinsic specificity of their target genes.
Carnac
G
G
Laboratoire de Diff erenciation Cellulaire et Crossiance, Institut National de la Recherche Agronomique, Montpellier, France.
Albagli-Curiel
O
O
Desclozeaux
M
M
Vandromme
M
M
Glineur
C
C
Bègue
A
A
Laudet
V
V
Bonnieu
A
A
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D051379:Mice; D009132:Muscles / Q000166:cytology* / Q000378:metabolism; D017570:MyoD Protein / Q000032:analysis; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011519:Proto-Oncogenes; D018168:Receptors, Retinoic Acid / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D014162:Transfection; D014284:Triiodothyronine / Q000494:pharmacology
D017570:MyoD Protein; D016755:Proto-Oncogene Proteins c-jun; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine