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

Abstract

The Friend-virus-derived 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). There 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. After DMSO induction, a biphasic decline in steady-state levels of c-myc and c-myb messenger RNAs occurs. Following the initial decrease in c-myc mRNA expression, the subsequent increase occurs in, and is restricted to, the G1 phase of the cell cycle. 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 transfected human c-myc gene inhibits the terminal differentiation process.

Max and inhibitory c-Myc mutants induce erythroid differentiation and resistance to apoptosis in human myeloid leukemia cells

“…This has been found in murine (M1, MEL, WEHI3B) and human cell lines (HL60, U937) (reviewed in Marcu et al, 1992). Consistently, constitutive expression of c-myc inhibits the chemically-induced di erentiation of some of these cell lines (Chisholm et al, 1992;Coppola and Cole, 1986;Dmitrovski et al, 1986;Larsson et al, 1988) and inhibition of c-myc expression induce di erentiation (Holt et al, 1988;Prochownik et al, 1988;Nguyen et al, 1995). Paradoxically, it has been shown that c-Myc overexpression induces apoptosis in di erent cell systems under conditions where c-Myc is normally down-regulated (reviewed in Harrington et al, 1994;Packham and Cleveland, 1995).…”

MAZ, a Myc-associated zinc finger protein, is essential for the ME1a1-mediated expression of the c-myc gene during neuroectodermal differentiation of P19 cells

“…The down-regulation of the cmyc gene in an essential component of di erentiation, as reported in other systems (Lachman et al, 1986;Prochownik and Kukowska, 1986;Yokoyama and Imamoto, 1987;WickstroÈ m et al, 1988;Holt et al, 1988). The constitutive expression of a transfected cmyc gene prevents the di erentiation of mouse erythroleukemia cells (Coppola and Cole 1986;Dmitrovsky et al, 1986;Lachman et al, 1986;Prochownik and Kukowska, 1986;Kume et al, 1988), but its critical function has not been well documented. Moreover, the biphasic transient accumulation of c-myc mRNA in P19 cells that have been treated with 1610 76 M RA appears to be well correlated with di erentiation in the neuroectodermal lineage Edwards and McBurney, 1983).…”

Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation

“…To examine more closely the relationship between c-Myc and TERT gene expression, we measured steady state c-myc and TERT mRNA levels following HMBA treatment in parental MEL cultures and in Myc56MEL cells, a well characterized MEL clonal derivative that constitutively expresses c-Myc (Dmitrovsky et al, 1986). As shown in Figure 1, Figure 1 Correlation between c-myc and TERT expression during induced di erentiation of MEL cells.…”

“…(a) MEL cells were induced to di erentiate by the addition of HMBA as described in Experimental procedures. The top panel shows RNAse protection analysis (RPA) for mTERT normalized to b-actin for 0, 2 and 4 h following HMBA addition for MEL and MEL clone 56 which constitutively expresses c-myc (Dmitrovsky et al, 1986). The middle panel shows a Northern blot of 20 mg total RNA derived from the same MEL samples used in the RPA and probed with a mouse c-myc cDNA fragment.…”

“…Lachman and Skoultchi (1984). The MEL cell line, Myc56, constitutively expressing human c-myc was a generous gift of Arthur Skoultchi (Dmitrovsky et al, 1986).…”