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 Cellsстатья
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Дата последнего поиска статьи во внешних источниках: 30 июня 2021 г.
Аннотация:In proliferating normal and tumor cells, the telomere length (TL) is maintained by high telomeraseactivity (TA). In the absence of TA the TL maintenance involves a mechanism of alternative lengthening oftelomeres (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 stemcells (MSCs) from mouse bone marrow, as well as in sarcomas that developed after transplantation of thesecells into syngeneic mice, and in fibrosarcoma cell lines obtained from these tumors. During prolonged cultivationof 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. Evena deeper decrease in TA was found in sarcomas developed after administration of transformed MSCs to syngeneicmice and in fibrosarcoma cell lines isolated from these tumors in which TA was either absent or wasfound to be at a very low level. In three of the four lines obtained TL was two times lower than in the initialMSCs. With absent or low TA and reduced TL, the cells of all the obtained fibrosarcoma lines successfullyproliferated without signs of altered survival. The mechanism of telomere maintainance in fibrosarcoma celllines in the absence of TA needs further investigation and it can be associated with involvement of the ALTpathway. The detected decrease or the absence of TA in irradiation-transformed MSCs with preserved or evenan 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 withoutTA can be a useful model for studying the efficacy of TA and ALT inhibitors in vitro and in vivo.