Possible role of c-fos, c-N-ras and c-mos proto-oncogenes in muscular development.

Time course analyses of various proto-oncogene transcripts compared with cytoskeleton-specific and muscle-specific messenger RNAs (mRNAs) were carried out during growth and differentiation of a clonal line of rat myoblasts that retain the capacity to form non-contractile fibres in vitro. Throughout their growth phase, these cells express consistent levels of c-fos, c-myc, c-Ki-ras and c-N-ras RNA and no c-mos RNA. When the cultures approach confluency the level of c-fos RNA rises sharply 3-4-fold, peaks, and rapidly declines when muscle-specific transcripts start accumulating, to become negligible in myotube-forming cells. These changes occur whatever the concentration in seric factors. By contrast, the level of c-N-ras RNA rises up to 3-fold and both c-myc and c-Ki-ras RNAs are slowly eliminated during the myogenic process, whereas no c-mos RNA is detectable. However, skeletal muscles from prenatal fetuses and adult animals were reproducibly found to contain both low and high levels of c-mos RNA respectively. These data and the demonstration that inactivation of the c-fos gene correlates with the loss of myogenic capability in six lines of neoplastic myoblasts, including four lines transformed by the v-fos oncogene, suggest a physiological function for this proto-oncogene during early stages of myogenesis and for the c-N-ras and c-mos genes in later stages of muscular development.