Type-1 insulin-like growth factor receptor overexpression produces dual effects on myoblast proliferation and differentiation.
Using a retroviral vector, we developed a line of C2 mouse skeletal myoblasts, C2-LISN, which expressed high levels of the human type-1 insulin-like growth factor (IGF) receptor. When switched to low serum medium, C2-LISN myoblasts underwent terminal differentiation extremely rapidly compared to control C2 myoblasts. In high serum conditions which were not permissive for differentiation, C2-LISN myoblasts expressed ten-fold higher levels of the myogenic transcription factor myogenin than did control C2 myoblasts. When cultured in low serum medium with both transforming growth factor-beta (TGF-beta) and high concentrations of IGF-I, C2-LISN myoblasts failed to differentiate and grew to very high saturation densities, forming multilayers. Upon removal of TGF-beta, multilayered C2-LISN myoblasts differentiated within 2 days. These results demonstrate that overexpression of the type-1 IGF receptor can amplify signals which stimulate myogenic differentiation. Overexpressed type-1 IGF receptors can also mediate strong mitogenic signals if differentiation is inhibited by TGF-beta. The C2-LISN myoblast cell line may be a useful model to investigate the intracellular pathways which stimulate myogenic differentiation. Additionally, overexpression of the type-1 IGF receptor could provide a strategy to expand populations of differentiation-competent myoblasts for experimental or clinical applications.
Quinn
L S
LS
Department of Biological Structure, University of Washington, Seattle 98195.
Steinmetz
B
B
Maas
A
A
Ong
L
L
Kaleko
M
M
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D009132:Muscles / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009218:Myosins / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000502:physiology*; D012518:Sarcomeres / Q000502:physiology / Q000648:ultrastructure; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D003470:Culture Media; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D009218:Myosins