Differential control of muscle-specific gene expression specified by src and myc oncogenes in myogenic cells.

Myogenic cells can be transformed in vitro by the introduction of several exogenous viral oncogenes. Transformed myoblasts are prevented from terminal differentiation into myotubes by the continuous expression of oncogenes such as myc and src, chosen as prototypes of nuclear and cytoplasmic oncogenes. A comparative analysis of the relationship between transformation and differentiation in myoblasts and cells belonging to other lineages has led to the proposal that terminal differentiation of myc-transformed quail myoblasts is indirectly prevented by the loss of growth control and that myc-bearing cells remain susceptible to growth regulation by interaction with adjacent normal cells. On the contrary, the src oncogene appears to affect expression of the myogenic programme via a direct mechanism, independent from abnormal growth control. There is increasing evidence for the existence of master regulatory genes that govern and influence muscle development in vivo and myogenic differentiation in vitro. Expression of cytoplasmic oncogenes such as src, ras and polyoma middle T in the mouse myogenic cell line, C2, results in inhibition of biochemical differentiation and a marked down-regulation of the MyoD1 and myogenin genes.