Density‐dependent arrest of DNA replication is accompanied by decreased levels of c‐myc mRNA in myogenic but not in differentiation‐defective myoblasts

Myoblasts from primary rat cultures and established mouse (Cl10) and rat (L6, Ama 420) cell lines were examined for c‐oncogene expression during exponential growth and under conditions which allowed myogenic differentiation. The abundance of c‐Ki‐ras transcripts in mRNA from confluent, quiescent cultures was reduced to 15–40% of that in mRNA from exponentially growing cells. This reduction was found both in primary myoblast cultures, myoblast lines that formed mytubes (L6 and Cl10) and in a differentiation defective subline (Ama 420). The level of c‐myc transcripts was lowered when myogenic rat L6 myoblasts reached a high cell density, stopped DNA synthesis and formed myotubes. At the same cell density, growth arrested myoblasts of differentiation defective Ama 420 cells maintained a high level of c‐myc expression. This shows that DNA replication and c‐myc expression are independently regulated. All myoblast lines also showed expression of c‐abl during exponential growth phase. Reduced expression was seen in differentiated L6 and Cl10 cultures. No expression was detected when mRNA from multiplying and differentiating myoblasts cultures were probed for c‐myb, c‐erbA, c‐erbB, c‐mos, c‐fes, and c‐src. The observations are consistent with a role for c‐Ki‐ras in myoblast proliferation and suggest that a reduction in c‐myc expression may be a necessary prerequisite for terminal myogenic differentiation.