Oct-1 modifies S100A4 exchange between intra- and extracellular compartments in Namalwa cells and increases their sensitivity to glucocorticoids
| Autor: | Natalia V. Soshnikova, A. S. Dukhanin, T. N. Portseva, A G Stepchenko, Sofia G. Georgieva, E V Pankratova, Dukhanina Ea |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
genetic structures Cell Survival Antineoplastic Agents Biology Transfection Dexamethasone Inhibitory Concentration 50 03 medical and health sciences Receptors Glucocorticoid Glucocorticoid receptor Report Cell Line Tumor Gene expression Extracellular medicine Humans Protein Isoforms S100 Calcium-Binding Protein A4 Molecular Biology B-Lymphocytes Cell Biology eye diseases Gene Expression Regulation Neoplastic Drug Combinations Protein Transport 030104 developmental biology DNA Topoisomerases Type I Tumor progression Cancer research Camptothecin sense organs Signal transduction Intracellular Octamer Transcription Factor-1 Plasmids Signal Transduction Developmental Biology medicine.drug |
| Zdroj: | Cell Cycle. 15:1471-1478 |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.1080/15384101.2016.1175260 |
| Popis: | S100A4, a small intra- and extracellular Ca(2+)-binding protein, is involved in tumor progression and metastasis with S100A4 level shown to be correlated with tumor cells metastatic potential. Simultaneously, Octamer transcription factor 1 (Oct-1) regulates a wide range of genes and participates in tumor cell progression with high Oct-1 level associated with a poor prognosis for different tumors. In this study, following the establishment of Oct-1 binding site, we used Burkit lymphoma B cells (Namalwa cells) which express different isoforms of Oct-1 (Oct-1A, Oct-1L and Oct-1X) to investigate the role of Oct-1 in S100A4 expression and sustaining intra- and extra-cellular S100A4 levels. As antitumor agents, we used dexamethasone which effect is mediated by the activation of intracellular glucocorticoid receptors and camptothecin which molecular target is nuclear DNA topoisomerase I (TOP1). We established that, firstly, the most significant increase in S100A4 gene expression has been demonstrated in the cells transfected with Oct-1A. Secondly, we have established that high level of Oct-1 and decreased intracellular S100A4 level decline the survival of Namalwa cells under dexamethasone treatment. Thirdly, we have shown that the tumor cells transformation by different Oct-1 isoforms retained those cells' sensitivity to the antitumor effect of combined dexamethasone and camptothecin. In contrast, in the non-transformed Namalwa cells, dexamethasone decreased the camptothecin effect on the cells survivorship, thus, emphasizing Oct-1 role in the regulation of cell response to different antitumor agents. The results identify a necessity to consider Oct-1 level for combined chemotherapeutic drug treatment. |
| Databáze: | OpenAIRE |
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