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

Abstract

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 regula tion of cellular processes in embryonic cells is largely unknown. In the present study, a comparative quanti tative 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 stim ulate 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 reg ulation of the Mage a gene expression and down regulation of Mage b gene expression. However, modula tion of the MEK/ERK signaling pathway activity and DNA demethylation with 5 azacytidine had no signif icant effects on the Mage a and Mage b gene expression in MEFs. The most essential changes in the expres sion 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.