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Expression of cancer-testis antigens of Mage-a and Mage-b families in mouse embryonic fibroblasts cultured in vitro

机译:Mage-a和Mage-b家族的睾丸癌抗原在体外培养的小鼠胚胎成纤维细胞中的表达

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摘要

Cancer-testis antigens are expressed in the spermatogenic and cancer cells, as well as in human and mouse pluripotent stem cells. However, the role of cancer-testis antigens of Mage families in the regulation of cellular processes in embryonic cells is largely unknown. In the present study, a comparative quantitative analysis of the Mage-a and Mage-b gene expression was performed in mouse embryonic somatic cells (mouse embryonic fibroblasts, MEFs) long-term cultured in vitro or exposed to factors that inhibit and stimulate proliferation. The analysis revealed a low expression of cancer-testis antigens of Mage families and showed that the decrease in proliferative activity of MEFs at late passages was accompanied by slight up-regulation of the Mage-a gene expression and down-regulation of Mage-b gene expression. However, modulation of the MEK/ERK-signaling pathway activity and DNA demethylation with 5-azacytidine had no significant effects on the Mage-a and Mage-b gene expression in MEFs. The most essential changes in the expression levels of Mage-a and Mage-b genes were found only when MEFs were exposed to mitomycin C. In all experimental variants, the predominant cytoplasmic localization of Mage antigens was found in MEFs at the DNA synthesis stage, as well as at other stages of the cell cycle. Presumably, in actively proliferating mouse embryonic somatic cells, the antigens of Mage-a and Mage-b families can act as coactivators in the regulation of cell proliferation and other cellular processes.
机译:睾丸抗原在生精细胞和癌细胞以及人和小鼠多能干细胞中表达。然而,Mage家族的睾丸癌抗原在调节胚胎细胞的细胞过程中的作用尚不清楚。在本研究中,在长期体外培养的小鼠胚胎体细胞(小鼠胚胎成纤维细胞,MEF)中或暴露于抑制和刺激增殖的因素下,对Mage-a和Mage-b基因表达进行了定量比较分析。分析显示,Mage家族的癌-睾丸抗原表达低,并且显示MEF在晚期传代中增殖活性的降低伴随着Mage-a基因表达的轻微上调和Mage-b基因的下调表达。但是,MEK / ERK信号通路活性的调节和5-氮杂胞苷对DNA的去甲基化作用对MEF中的Mage-a和Mage-b基因表达没有显着影响。仅当MEF暴露于丝裂霉素C时,才会发现Mage-a和Mage-b基因表达水平的最本质变化。在所有实验变体中,在DNA合成阶段,MEF中都发现了Mage抗原的主要细胞质定位,以及细胞周期的其他阶段。据推测,在活跃增殖的小鼠胚胎体细胞中,Mage-a和Mage-b家族的抗原可以在细胞增殖和其他细胞过程的调节中充当共激活因子。

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