Department of Life Sciences, University of Trieste, Trieste, Italy.
Hematol Oncol. 2013 Jun;31(2):110-6. doi: 10.1002/hon.2022. Epub 2012 Aug 29.
The elongation factor 1A proteins (eEF1A1/A2) are known to play a role in tumours. We previously found that a more basic isoform of eEF1A (MBI-eEF1A) is present in the cytoskeletal/nuclear-enriched extracts of CCRF-CEM T-lymphoblasts but not in those of normal lymphocytes. To obtain deeper knowledge about MBI-eEF1A biology, we investigate from which of the eEF1A proteins, eEF1A1 or eEF1A2, MBI-eEF1A originates and the possibility that its appearance can be modulated by the differentiated or proliferative cell status. CCRF-CEM T-lymphoblasts and normal lymphocytes were cultured with or without differentiation/pro-proliferative stimuli (Phorbol 12-Myristate 13-Acetate (PMA) alone or the combination of phytohaemagglutinin (PHA) with PMA, respectively), and the presence of MBI-eEF1A evaluated together with that of the eEF1A1/A2 mRNAs. Our data indicate that the MBI-eEF1A may derive from eEF1A1 as eEF1A2 is not expressed in CCRF-CEM and normal lymphocytes. Moreover, MBI-eEF1A is inducible in normal lymphocytes upon hyper-proliferative stimuli application; in CCRF-CEM, its presence can be abrogated by PMA-induced differentiation. Finally, MBI-eEF1A may have a functional role in hyper-proliferating/tumour cells as its disappearance reduces the growth of CCRF-CEM and that of PHA/PMA-stimulated lymphocytes. The presented data suggest that MBI-eEF1A may be related to oncogenic cell phenotype, rising the possibility to use MBI-eEF1A as target for novel therapeutic strategies.
延伸因子 1A 蛋白(eEF1A1/A2)已知在肿瘤中发挥作用。我们之前发现,在 CCRF-CEM T 淋巴细胞的细胞骨架/核富集提取物中存在一种碱性同工型 eEF1A(MBI-eEF1A),但在正常淋巴细胞中不存在。为了更深入地了解 MBI-eEF1A 的生物学特性,我们研究了 MBI-eEF1A 源自哪种 eEF1A 蛋白(eEF1A1 或 eEF1A2),以及其出现是否可以通过分化或增殖细胞状态进行调节。将 CCRF-CEM T 淋巴细胞和正常淋巴细胞在有或没有分化/促增殖刺激物(单独使用佛波醇 12-肉豆蔻酸 13-乙酸酯(PMA)或植物血球凝集素(PHA)与 PMA 的组合)的情况下培养,并评估 MBI-eEF1A 的存在与 eEF1A1/A2mRNA 的存在。我们的数据表明,MBI-eEF1A 可能源自 eEF1A1,因为 eEF1A2 在 CCRF-CEM 和正常淋巴细胞中不表达。此外,在应用高增殖刺激物时,MBI-eEF1A 可在正常淋巴细胞中诱导产生;在 CCRF-CEM 中,其存在可被 PMA 诱导的分化所消除。最后,MBI-eEF1A 可能在高增殖/肿瘤细胞中具有功能作用,因为其消失会降低 CCRF-CEM 和 PHA/PMA 刺激的淋巴细胞的生长。所呈现的数据表明,MBI-eEF1A 可能与致癌细胞表型有关,这增加了将 MBI-eEF1A 用作新型治疗策略的靶标的可能性。