Expression of a transfected human c-myconcogene inhibits differentiation of a mouse erythroleukaemia cell line

The Friend-virus-derived¹ mouse erythroleukaemia (MEL) cell lines represent transformed early erythroid precursors that can be induced to differentiate into more mature erythroid cells by a variety of agents including dimethyl sulphoxide (DMSO)²There is a latent period of 12 hours after inducer is added, when 80-90% of the cells become irreversibly committed to the differentiation programme, undergoing several rounds of cell division before permanently ceasing to replicate^3,4. After DMSO induction, a biphasic decline in steady-state levels of c-myc ^5,6 and c-myb ⁶ messenger RNAs occurs. Following the initial decrease in c-myc mRNA expression, the subsequent increase occurs in, and is restricted to, the G_l phase of the cell cycle⁷. We sought to determine whether the down-regulation is a necessary step in chemically induced differentiation. Experiments reported here indicate that expression in MEL cells of a transf ected human c-myc gene inhibits the terminal differentiation process.