Translational upregulation of the c-myc oncogene in Bloom's 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 overexpression results from a specific increase in the translation of the c-myc mRNA and is not the result of either a chromosomal translocation involving the c-myc locus or an amplification of this gene. We also did not detect any increase in the stability of the c-myc protein or any significant increases in the levels of c-myc mRNA expressed in BS cells compared 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 have also examined the levels of these proteins in BS cells and found them to be either comparable or lower than those in control cell lines. These data suggest that if c-myc does contribute to the cancer predisposition phenotype in BS then it does not appear to act via an eIF-4E and eIF-2 alpha mediated pathway.
Department of Biochemistry, University of Leicester, UK.
M J
MJ
West
N F
NF
Sullivan
A E
AE
Willis
D001816:Bloom Syndrome / Q000235:genetics*; D002460:Cell Line; D015852:Eukaryotic Initiation Factor-2 / Q000032:analysis; D039561:Eukaryotic Initiation Factor-4E; D005784:Gene Amplification; D016259:Genes, myc; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D010448:Peptide Initiation Factors / Q000032:analysis; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D014178:Translocation, Genetic; D015854:Up-Regulation
D015852:Eukaryotic Initiation Factor-2; D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases