West M J, Sullivan N F, Willis A E
Department of Biochemistry, University of Leicester, UK.
Oncogene. 1995 Dec 21;11(12):2515-24.
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.
先前的研究表明，源自易患癌症的布卢姆综合征（BS）患者的细胞系中，c-myc蛋白水平呈组成性增加。我们在此报告，这种过表达是由于c-myc mRNA翻译的特异性增加所致，而非涉及c-myc基因座的染色体易位或该基因扩增的结果。与对照细胞系相比，我们也未检测到BS细胞中c-myc蛋白稳定性的任何增加或c-myc mRNA水平的任何显著增加。总体而言，BS细胞系中c-myc mRNA与多核糖体的结合增加了39%-80%。由于在某些情况下，c-myc蛋白的过表达已被证明会增加翻译起始因子eIF-4E和eIF-2α的水平，而这两者本身可能在恶性转化中起作用，我们还检测了BS细胞中这些蛋白的水平，发现它们与对照细胞系中的水平相当或更低。这些数据表明，如果c-myc确实导致了BS的癌症易感性表型，那么它似乎并非通过eIF-4E和eIF-2α介导的途径发挥作用。
