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Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells

BIOcell 2021年第5期45卷 1355-1367页

作者： ISIDORA PETROVIC MILENA MILIVOJEVIC ANA ARSENIJEVIC ANDRIJANA LAZIC NATASA KOVACEVIC GRUJICIC MARIJA SCHWIRTLICH JELENA POPOVIC MILENA STEVANOVIC Institute of Molecular Genetics and Genetic Engineering University of BelgradeBelgradeSerbia Institute of cell Biology School of Biological SciencesThe University of EdinburghEdinburghUK Department of Radiation Oncology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Faculty of Biology University of BelgradeBelgradeSerbia Serbian Academy of Sciences and Arts BelgradeSerbia

Genetic and molecular heterogeneity,together with intrinsic and acquired resistance to therapy,represent the major obstacles to the successful treatment of different types of breast *** evidence demonstrates that SOX transcription factors in breast carcinomas could act both as oncogenes and tumor suppressors and have been associated with tumor stage and grade,poor prognosis,and therapy *** SOX2 and SOX18 overexpression has been correlated with poor prognosis in breast carcinomas,and these genes are recognized as potential antitumor *** aim was to evaluate the effect of retinoic acid(RA),a well-known cyto-differentiating agent,on breast carcinoma cells in vitro and to investigate the potential of RA treatment to modify the expression of SOX2 and SOX18 *** applying various experimental approaches,we evaluated the effect of RA on basic cellular processes in SK-BR-3 and mcf7 breast carcinoma cell *** have shown that RA inhibits cell growth,reduces the number of Ki-67 positive cells,and causes cell-cycle *** effect was more prominent in SK-BR-3 cell line that lacks SOX2 expression,including a higher decrease in cell viability,reduction in colony formation,and significant remodeling of cellular *** have shown that RA treatment led to the downregulation of SOX2 expression in mcf7 cells and to the reduction of SOX18 expression in both cell *** functional analysis,we showed that the anti-proliferative effect of RA in both cell lines was not based on the activity of stemness marker SOX2,pointing to a SOX2-independent mechanism of *** ability of RA to reduce SOX2/SOX18 expression raises the possibility that these genes can be used as biomarkers to distinguish RA-responders from ***,our study shows that the response of breast carcinoma cell lines to RA treatment may vary,highlighting that the development of RA-based therapy should consider differences in breast carcinoma subtypes.

关键词： Breast carcinoma Anti-proliferative activity Transcription factors mcf7 cell line SK-BR-3 cell line

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