Deregulated expression of c-myc by murine erythroleukaemia cells prevents differentiation

Abstract

Friend murine erythroleukaemia (F-MEL) cells are a permanent line of primitive erythroid precursors originally derived from the spleens of mice infected with the Friend strain of murine leukaemia virus. F-MEL cells differentiate in vitro in response to various chemical inducers. Concomitantly with induction, a biphasic regulation of c-myc oncogene transcripts is observed. Within one hour of the addition of dimethyl sulphoxide (DMSO) or hypoxanthine (Hyp), the levels of c-myc transcripts fall dramatically and remain virtually undetectable for the next few hours. Between 8 and 24 hours after induction, c-myc transcripts return to pre-induction levels and then decline again between 3 and 5 days as most of the cells undergo terminal differentiation. To explore the potential relationship between c-myc expression and F-MEL terminal differentiation, we have investigated here whether reversing the early fluctuations in c-myc transcript levels affects the ability of F-MEL cells to differentiate. We therefore constructed an amplifiable plasmid vector containing a full-length mouse c-myc complementary DNA and introduced it stably into recipient F-MEL cells. The exogenous c-myc sequences are transcribed in F-MEL cells and the transcript levels do not change significantly in response to inducing agents. The net result is continued c-myc expression following DMSO or Hyp induction and a complete or partial inhibition of F-MEL differentiation.