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Type‐1 insulin‐like growth factor receptor overexpression produces dual effects on myoblast proliferation and differentiation
Author(s) -
Quinn Lebris S.,
Steinmetz Brian,
Maas Adolf,
Ong Luan,
Kaleko Michael
Publication year - 1994
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041590302
Subject(s) - myocyte , myogenin , growth factor , microbiology and biotechnology , c2c12 , biology , receptor , insulin like growth factor , endocrinology , transforming growth factor , medicine , chemistry , myogenesis , genetics
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‐β (TGF‐β) 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‐β, 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‐β. 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. © 1994 wiley‐Liss, Inc.