Exogenous c-myc gene overexpression interferes with early events in F9 cell differentiation

The effect of c-myc gene expression on F9 teratocarcinoma stem cell differentiation was studied by transfecting mouse metallothionein I promoter-driven human c-myc genes into F9 cells. Human c-myc gene expression was triggered by cadmium treatment at different stages of differentiation. When this expression was induced before or just after addition of retinoic acid plus cyclic AMP (RA +cAMP), the death of 70-80% of the cells was observed. This cell mortality was not observed either when the parental F9 cells were induced to differentiate in the presence of cadmium or when the undifferentiated transfected clone was permanently grown in the presence of this inducer. The 30% surviving cells underwent terminal differentiation despite high c-myc mRNA levels and expressed differentiation-specific genes normally like their parental F9 cells. When cadmium was added 24 or 48 hr after RA +cAMP, no cell mortality or any other detectable effect on differentiation were observed, even though c-myc gene transcripts were induced. We therefore conclude that c-myc gene expression only inhibits F9 differentiation at an early stage in 70-80% of cells. The significance of these results will be discussed.