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Information × Registration Number 0226U002667, (0124U000078) , R & D reports Title Stress-induced factors of the negative microenvironment as risk drivers of breast cancer progression (code: 2.2.5.460) popup.stage_title В експериментах in vitro дослідити зміни співвідношення генів матриксинів під впливом екзогенних факторів хронічного стресу у клітинах РМЗ людини різного ступеня злоякісності. Head Luk'ianova Nataliia Yu., Доктор біологічних наукChekhun Vasyl F., Доктор медичних наук Registration Date 03-03-2026 Organization R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology National Academy of Sciences of Ukraine popup.description1 To identify the expression pattern of stress-induced factors of the tumor microenvironment and to substantiate the feasibility of their use to assess the risk of breast cancer progression. popup.description2 In an in vitro system, two models of chronic stress were developed and validated for human breast cancer cells of high and low degrees of malignancy using dexamethasone and adrenaline. As a result of the analysis of molecular and biological characteristics of the cells, it was determined that in the low-grade breast cancer cell line, adrenaline predominantly inhibits the expression of MMP genes, whereas in high-grade malignant cells it, conversely, activates their transcription, thereby promoting an increase in invasive potential and remodeling of the extracellular matrix via the involvement of the cAMP/PKA and MAPK signaling cascades. It was established that dexamethasone exerts divergent effects on matrix metalloproteinase expression in breast cancer cells: it stimulates collagenolytic and gelatinase activity in low-grade malignant MCF-7 cells and suppresses most of these activities in high-grade malignant MDA-MB-231 cells, which is likely determined by the specific features of glucocorticoid receptor interactions with the transcription factors AP-1 and NF-κB. The action of dexamethasone was also accompanied by a decrease in TIMP3 expression in low-grade malignant MCF-7 cells and its increase in high-grade malignant MDA-MB-231 breast cancer cells. It was found that changes in the expression of microRNAs involved in the post-transcriptional regulation of matrix metalloproteinases, in MCF-7 cells are limited and predominantly unidirectional with a more pronounced effect of dexamethasone. In high-grade malignant cells, both adrenaline and dexamethasone induced multidirectional changes in microRNA expression profiles, indicating high regulatory plasticity and reprogramming of mechanisms associated with MMP/TIMP-dependent matrix remodeling. The identified panels of stress-dependent matrix metalloproteinases and their tissue inhibitors may be used to predict the aggressiveness of the clinical course of breast cancer. Product Description popup.authors Igor M. Todor Lesia A. Nalieskina Voronina Olena K Taras V. Zadvornyi Anna O. Pavlova Liubov M. Kunska Iryna V. Shepelenko Tetiana S. Burda Nataliia M. Panchul Koziaruk Anastasiia A. Anastasiia O. Shevchuk Bazas Volodymyr M. Sofiia I. Suslova Mariia O. Yeshchenko Anastasiia Y. Levenets Mariia V. Kokoilo popup.nrat_date 2026-03-03 Close