Grassi G, Scaggiante B, Farra R, Dapas B, Agostini F, Baiz D, Rosso N, Tiribelli C
Department of Clinical, Morphological and Technological Sciences, Division of Internal Medicine, University of Trieste, Via Giorgieri, 1, 34127 Trieste, Italy.
Biochimie. 2007 Dec;89(12):1544-52. doi: 10.1016/j.biochi.2007.07.007. Epub 2007 Jul 20.
Despite the involvement of the elongation factors eEF1A (eEF1A1 and eEF1A2) in the development of different cancers no information is available on their possible contribution to the biology of hepatocellular carcinoma (HCC). We investigated the expression of both forms of eEF1A in HepG2 and JHH6 cell lines considered to be a good in vitro model of HCC at different stage of differentiation. Our data indicate that the mRNA amount of eEF1A1 is increased in both cell lines as compared to normal liver tissue, but eEF1A2 mRNA level is markedly increased only in JHH6. Moreover, the less differentiated cell line JHH6 displays higher EEF1A1 and EEF1A2 mRNAs levels and an higher nuclear-enriched/cytoplasm ratio of EEF1A protein compared to the better differentiated HepG2 cell line. Over-expression depends only partially on gene amplification. The more abundant mRNA levels and the higher nuclear-enriched/cytoplasm ratio of eEF1A in JHH6 neither correlate with apoptosis resistance nor with proliferation rate in sub-confluent cells. However, in confluent cells, a clear tendency to maintain JHH6 into the cell cycle was observed. In conclusion, we document the increased mRNA levels of EEF1A genes in HCC cell lines compared to normal liver. Additionally, we show the increased nuclear-enriched/cytoplasmic protein ratio of eEF1A and the marked raise of the expression of both eEF1A forms in JHH6 compared to HepG2, suggesting the possibility that eEF1A forms might become a relevant markers related to HCC tumor phenotype.
尽管延伸因子eEF1A(eEF1A1和eEF1A2)参与了不同癌症的发展,但关于它们对肝细胞癌(HCC)生物学的可能贡献尚无相关信息。我们研究了eEF1A两种形式在HepG2和JHH6细胞系中的表达,这两种细胞系被认为是不同分化阶段HCC的良好体外模型。我们的数据表明,与正常肝组织相比,两种细胞系中eEF1A1的mRNA量均增加,但eEF1A2的mRNA水平仅在JHH6中显著增加。此外,与分化较好的HepG2细胞系相比,分化较差的细胞系JHH6显示出更高的EEF1A1和EEF1A2 mRNA水平以及更高的EEF1A蛋白核富集/细胞质比率。过表达仅部分依赖于基因扩增。JHH6中eEF1A更丰富的mRNA水平和更高的核富集/细胞质比率与亚汇合细胞中的抗凋亡能力或增殖率均无相关性。然而,在汇合细胞中,观察到JHH6有明显维持在细胞周期中的趋势。总之,我们记录了与正常肝脏相比,HCC细胞系中EEF1A基因的mRNA水平增加。此外,我们显示了eEF1A核富集/细胞质蛋白比率增加,并且与HepG2相比,JHH6中两种eEF1A形式的表达显著升高,这表明eEF1A形式可能成为与HCC肿瘤表型相关的重要标志物。