Several studies have shown that neuroblastoma and retinoblastoma tumor cells often have elevated N-myc mRNA levels compared to normal adult neuronal or retinal tissues, and it has been suggested that increased expression of this protooncogene may play an important role in tumorigenesis or malignant progression in cells of neural origin. We have studied the effect of protein synthesis inhibitors on the N-myc mRNA levels in Y79 retinoblastoma and LA-N-5 neuroblastoma cells. We showed that when new RNA synthesis was inhibited by actinomycin D the levels of existing N-myc mRNA fell rapidly in both cell lines relative to total cytoplasmic RNA. The half-life for N-myc mRNA was approximately 30 min. Inhibition of protein synthesis by interfering with polypeptide elongation or by inhibiting initiation of protein synthesis increased the levels of N-myc mRNA at least 3-fold after 4 hours. Nuclear runoff transcription experiments showed that the protein synthesis inhibitors did not alter N-myc transcription rates. Combined actinomycin D treatment and treatment with protein synthesis inhibitors indicated that this increase in N-myc transcript levels was due to an increase in the N-myc mRNA lifetimes. Thus, N-myc transcript levels increased because they were more stable in protein synthesis-inhibited cells. Protein synthesis inhibition also increased c-myc mRNA levels in HL-60 human promyelocytic leukemia cells, but no increase was seen in the relatively low level of c-myc mRNA in protein synthesis-inhibited neuronal tumor cells. These results support the hypothesis that the regulation of N-myc in these neuronal and retinal tumor cells is similar to that of c-myc in other tumor types.

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This work was supported by the Office of Energy Research, Office of Health and Environmental Research, Health Effects Research Division of the United States Department of Energy under Contract DE-AC03-76SF00098.

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