P. S. Parfenova, P. I. Deryabin, D. Yu. Pozdnyakov, A. V. Borodkina
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引用次数: 0
Abstract
One protective mechanism against neoplastic transformation of cells in response to oncogenic stimuli is cellular senescence. However, the ability of cells to activate this protective reaction depends on their nature and is not characteristic of all cell types. In this study, we studied the response of human endometrial stromal cells (EnSC-EnSC) to a classic oncogenic stimulus—inactivation of the tumor suppressor PTEN. Using CRISPR/Cas9 targeted genome editing technology, we were able to obtain an EnSC line with PTEN gene knockout. We showed that a decrease in the expression of PTEN leads to loss of proliferative activity, hypertrophy, accumulation of lipofuscin, and disruption of the redox balance of cells. The totality of the identified signs testifies in favor of the induction of premature senescence in EnSCs with PTEN knockout. When studying the molecular mechanisms, we established the key role of the PI3K/AKT signaling pathway in the implementation of the EnSC senescence program under conditions of PTEN knockout. Inhibition of this signaling pathway using the substance LY294002 prevented both the phenotypic manifestations of premature senescence and cell cycle arrest in PTEN-cell knockout. Thus, the development of premature senescence in conditions of reduced expression of the PTEN tumor suppressor can be considered a protective mechanism that prevents the malignant transformation of EnSCs.
期刊介绍：
The journal publishes papers on vast aspects of cell research, including morphology, biochemistry, biophysics, genetics, molecular biology, immunology. The journal accepts original experimental studies, theoretical articles suggesting novel principles and approaches, presentations of new hypotheses, reviews highlighting major developments in cell biology, discussions. The main objective of the journal is to provide a competent representation and integration of research made on cells (animal and plant cells, both in vivo and in cell culture) offering insight into the structure and functions of live cells as a whole. Characteristically, the journal publishes articles on biology of free-living and parasitic protists, which, unlike Metazoa, are eukaryotic organisms at the cellular level of organization.
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