TRANSLATIONAL UP-REGULATION OF THE C-MYC ONCOGENE IN BLOOMS SYNDROME CELL-LINES

Previous studies have shown a constitutive increase in the levels of c -myc protein in cell lines derived from patients with the cancer-prone disorder Bloom's Syndrome (BS), We report here that this overexpressi on results from a specific increase in the translation of the c-myc mR NA and is not the result of either a chromosomal translocation involvi ng the c-myc locus or an amplification of this gene, We also did not d etect any increase in the stability of the c-myc protein or any signif icant increases in the levels of c-myc mRNA expressed in BS cells comp ared to control cell Lines, Overall, there is a 39-80% increase in the association of the c-myc mRNA with polysomes in BS cell lines, Since, in some cases, overexpression of the c-myc protein has been shown to increase levels of the translation initiation factors eIF-4E and eIF-2 alpha, which may themselves play a role in malignant conversion, we h ave also examined the levels of these proteins in BS cells and found t hem to be either comparable or lower than those in control cell lines, These data suggest that if c-myc does contribute to the cancer predis position phenotype in BS then it does not appear to act via an eIF-4E and eIF-2 alpha mediated pathway.