Telomerase activity, mTert gene expression and the telomere length in mouse mesenchymal stem cells in the late period after γ- and γ,n-irradiation and in the tumors developed from these cells

   
Vysotskaya O.V.1, Glukhov A.I.2, Semochkina Yu.P.1, Gordeev S.A.3, Moskaleva E.Yu.1

1. NRC Kurchatov Institute, Moscow, Russia
2. Faculty of Biology, Moscow State University, Moscow, Russia; Sechenov University, Moscow, Russia
3. Faculty of Biology, Moscow State University, Moscow, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20206603265      PubMed Id: 32588833
Year: 2020  Volume: 66  Issue: 3  Pages: 265-273
In proliferating normal and tumor cells, the telomere length (TL) is maintained by high telomerase activity (TA). In the absence of TA the TL maintenance involves a mechanism of alternative lengthening of telomeres (ALT). The aim of this study was to investigate the level of TA, the mTert expression and TL in cultured normal and transformed by γ- and γ,n-irradiation mesenchymal stem cells (MSCs) from mouse bone marrow, in sarcomas that developed after the transplantation of these cells into syngeneic mice, and in fibrosarcoma cell lines obtained from these tumors to find out the role of AT or ALT in maintaining TL in these cells. During prolonged cultivation of normal and transformed under the influence of γ- (1 Gy and 6 Gy) and γ,n-irradiation (0.05 Gy, 0.5 Gy, and 2 Gy) MSCs from mouse bone marrow, a decrease in TA was detected in irradiated cells. Even deeper decrease in TA was found in sarcomas developed after administration of transformed MSCs to syngeneic mice and in fibrosarcoma cell lines isolated from these tumors in which TA was either absent or was found to be at a very low level. TL in three of the four lines obtained was halved compared to the initial MSCs. With absent or low TA and reduced TL, the cells of all the obtained fibrosarcoma lines successfully proliferated without signs of a change in survival. The mechanism of telomere maintainance in fibrosarcoma cell lines in the absence of TA needs further investigation and it can be assumed that it is associated with the use of the ALT. The detected decrease or absence of TA in transformed under the action of irradiation MSCs with the preservation or even an increase in the telomerase gene expression may be associated with the formation of inactive splicing variants, and requires further study. The obtained lines of transformed MSCs and fibrosarcomas with TA and without the activity of this enzyme can be a useful model for studying the efficacy of TA and ALT inhibitors in vitro and in vivo.
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Keywords: telomerase, gene expression, telomeres, alternative lengthening of the telomeres, mesenchymal stem cells, sarcoma
Citation:

Vysotskaya, O. V., Glukhov, A. I., Semochkina, Yu. P., Gordeev, S. A., Moskaleva, E. Yu. (2020). Telomerase activity, mTert gene expression and the telomere length in mouse mesenchymal stem cells in the late period after γ- and γ,n-irradiation and in the tumors developed from these cells. Biomeditsinskaya khimiya, 66(3), 265-273.
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