Expression of ER-resident selenoproteins and activation of cancer cells apoptosis mechanisms under ER-stress conditions caused by methylseleninic acid.

The aim of this work was to study changes in gene expression levels of 7 ER-resident selenoproteins under ER-stress caused by the action of a selenium-containing compound of organic nature, methylselenic acid using three human cancer cell lines DU 145 (prostate carcinoma), MCF 7 (breast adenocarcinoma)and HT-1080 (fibrosarcoma). According to the obtained results, we can speak of a synchronous changes in the expression of SELT and SEP15 mRNA depending on the concentration of MSA for 24 h, while the pattern of SELM expression was completely opposite and was radically different from other selenoproteins. It should be noted that in HT-1080 cells, the expression pattern of SELM differed from the expression pattern in two other cancer cells, while the expression patterns of other ER-resident selenoproteins (SELT, SEP15, SELK, SELS, SELN and DIO2) differed slightly depending on the cell line. Also we investigated the molecular mechanisms of UPR caused by MSA-induced ER stress in three cancer cell lines. According to the obtained results, it can be assumed that in DU 145 cells, MSA promotes activation of the PERK signaling pathway of UPR. In fibrosarcoma cells MSA was promoted the activation of ATF-6 UPR signaling pathway. In MCF 7 cells, MSA promoted the activation of two pro-apoptotic UPR signaling pathways at once: IRE1 and ATF-6.The results of this work once again demonstrate that the mechanisms of ER-stress regulation caused by the same agent, in this case, MSA, lead to the activation of different UPR signaling pathways in different cancer cells, and about their relationship.