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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 Tumors Developed from These Cells

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Abstract

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). In order to investigate the role of TA or ALT in maintaining TL we studied the level of TA, mTert expression, and TL in cultivated normal and transformed by γ- and γ,n-irradiation mesenchymal stem cells (MSCs) from mouse bone marrow, as well as in sarcomas that developed after transplantation of these cells into syngeneic mice, and in fibrosarcoma cell lines obtained from these tumors. 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 the irradiated cells. Even a 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. In three of the four lines obtained TL was two times lower than in the initial MSCs. With absent or low TA and reduced TL, the cells of all the obtained fibrosarcoma lines successfully proliferated without signs of altered survival. The mechanism of telomere maintainance in fibrosarcoma cell lines in the absence of TA needs further investigation and it can be associated with involvement of the ALT pathway. The detected decrease or the absence of TA in irradiation-transformed MSCs with preserved or even an increased in the telomerase gene expression may be associated with the formation of inactive splice variants, and requires further study. The obtained lines of transformed MSCs and fibrosarcomas with and without TA can be a useful model for studying the efficacy of TA and ALT inhibitors in vitro and in vivo.

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Funding

This work was supported by the National Research Center Kurchatov Institute (order no. 1363 of June 25, 2019).

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Authors and Affiliations

  1. National Research Center Kurchatov Institute, pl. Akademika Kurchatova 1, 123182, Moscow, Russia

    O. V. Vysotskaya, Yu. P. Semochkina & E. Yu. Moskaleva

  2. Faculty of Biology, Moscow State University, 119234, Moscow, Russia

    A. I. Glukhov & S. A. Gordeev

  3. Sechenov University, ul. Trubetskaya 8-2, 119991, Moscow, Russia

    A. I. Glukhov

Authors
  1. O. V. Vysotskaya
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  2. A. I. Glukhov
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  3. Yu. P. Semochkina
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  4. S. A. Gordeev
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  5. E. Yu. Moskaleva
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Corresponding author

Correspondence to E. Yu. Moskaleva.

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COMPLIANCE WITH ETHICAL STANDARDS

All experiments with animals were carried out in accordance with the “Rules for conducting work with the use of experimental animals” (Order of the USSR Ministry of Public Health no. 755 of December 8, 1977) and the requirements of the Ethical Committee of the National Research Center Kurchatov Institute on biomedical research.

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The authors declare that they have no conflict of inte-rest.

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Translated by A. Medvedev

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Vysotskaya, O.V., Glukhov, A.I., Semochkina, Y.P. et al. 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 Tumors Developed from These Cells. Biochem. Moscow Suppl. Ser. B 15, 80–88 (2021). https://doi.org/10.1134/S199075082101008X

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  • DOI: https://doi.org/10.1134/S199075082101008X

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