Oct-1 modifies S100A4 exchange between intra- and extracellular compartments in Namalwa cells and increases their sensitivity to glucocorticoids.
Cell Cycle
; 15(11): 1471-8, 2016 06 02.
Article
em En
| MEDLINE
| ID: mdl-27096393
ABSTRACT
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.
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MEDLINE
Assunto principal:
Camptotecina
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Dexametasona
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Regulação Neoplásica da Expressão Gênica
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Fator 1 de Transcrição de Octâmero
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Proteína A4 de Ligação a Cálcio da Família S100
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Antineoplásicos
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article