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 my oblasts, C2-LISN, which expressed high levels of the human type-1 insu lin-like growth factor (IGF) receptor. When switched to low serum medi um, C2-LISN myoblasts underwent terminal differentiation extremely rap idly compared to control C2 myoblasts. In high serum conditions which were not permissive for differentiation, C2-LISN myoblasts expressed t en-fold higher levels of the myogenic transcription factor myogenin th an did control C2 myoblasts. When cultured in low serum medium with bo th transforming growth factor-beta (TGF-beta) and high concentrations of IGF-1, C2-LISN myoblasts failed to differentiate and grew to very h igh saturation densities, forming multilayers. Upon removal of TGF-bet a, 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. Overexpress ed type-1 IGF receptors can also mediate strong mitogenic signals if d ifferentiation is inhibited by TGF-beta. The C2-LISN myoblast cell lin e may be a useful model to investigate the intracellular pathways whic h 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 a pplications. (C) 1994 Wiley-Liss, Inc.