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TG-interacting Factor(TGIF) Downregulates SOX3 Gene Expression in the NT2/D1 Cell Line

Journal of Genetics and Genomics 2012年第1期39卷 19-27页

作者： Marija Mojsin Jelena Popovic natasa kovacevic grujicic Milena Stevanovic Laboratory for Human Molecular Genetics Institute of Molecular Genetics and Genetic EngineeringUniversity of BelgradeVojvode Stepe 444aPO Box 2311010 BelgradeSerbia

SOX3 is a member of the Sox gene family implicated in brain formation and cognitive function. It is considered to be one of the earliest neural markers in vertebrates, playing a role in specifying neuronal fate. Recently, we have established the first link between TALE （three- amino-acid loop extension） proteins, PBX1 （pre-B-cell leukemia homeobox 1） and MEIS1 （myeloid ecotropic viral integration site 1 homologue）, and the expression of the human SOX3 gene. Here we present the evidence that TGIF （TG-interacting factor） is an additional TALE superfamily member involved in the regulation of human SOX3 gene expression in NT2/D1 cells by direct interaction with the consensus binding site that is conserved in primate orthologue promoters. Functional analysis demonstrated that mutation of the TGIF binding site resulted in the activation of SOX3 promoter. TGIF overexpression downregulates SOX3 promoter activity and decreases endogenous SOX3 protein expression in both uninduced and retinoic acid （RA）-induced NT2/D1 ceils. Up to now, this is the first transcription factor identified as a negative regulator of SOX3 gene expression. The obtained results further underscore the significance of TALE proteins as important transcriptional regulators of SOX3 gene expression.

关键词： NT2/D1 cells TGIF Retinoic acid SOX3

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SOX transcription factors and glioma stem cells:Choosing between stemness and differentiation

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World Journal of Stem Cells 2021年第10期13卷 1417-1445页

作者： Milena Stevanovic natasa kovacevic-grujicic Marija Mojsin Milena Milivojevic Danijela Drakulic Laboratory for Human Molecular Genetics Institute of Molecular Genetics and Genetic EngineeringUniversity of BelgradeBelgrade 11042Serbia Chair Biochemistry and Molecular Biology Faculty of BiologyUniversity of BelgradeBelgrade 11158Serbia Department of Chemical and Biological Sciences Serbian Academy of Sciences and ArtsBelgrade 11000Serbia

Glioblastoma(GBM)is the most common,most aggressive and deadliest brain ***,remarkable progress has been made towards understanding the cellular and molecular biology of *** tumor initiation,progression and relapse as well as resistance to treatments are associated with glioma stem cells(GSCs).GSCs exhibit a high proliferation rate and self-renewal capacity and the ability to differentiate into diverse cell types,generating a range of distinct cell types within the tumor,leading to cellular *** tumors may contain different subsets of GSCs,and some of them may adopt a quiescent state that protects them against chemotherapy and *** enriched in recurrent gliomas acquire more aggressive and therapy-resistant properties,making them more malignant,able to rapidly *** impact of SOX transcription factors(TFs)on brain tumors has been extensively studied in the last *** all SOX genes are expressed in GBM,and their expression levels are associated with patient prognosis and *** SOX TFs are involved in the maintenance of the stemness of GSCs or play a role in the initiation of GSC *** fine-tuning of SOX gene expression levels controls the balance between cell stemness and ***,innovative therapies targeting SOX TFs are emerging as promising tools for combatting *** GBM has been a demanding and challenging goal for *** current therapeutic strategies have not yet provided a cure for GBM and have only resulted in a slight improvement in patient *** approaches will require the fine adjustment of multimodal therapeutic strategies that simultaneously target numerous hallmarks of cancer cells to win the battle against GBM.

关键词： Glioblastoma SOX transcription factors Glioma stem cells Stemness Differentiation

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

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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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