Oct-1 modifies S100A4 exchange between intra- and extracellular compartments in Namalwa cells and increases their sensitivity to glucocorticoids.
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.
a Department of Transcription Factors , Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Moscow , Russia.
Elena A
EA
Dukhanina
a Department of Transcription Factors , Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Moscow , Russia.
Tatiana N
TN
Portseva
a Department of Transcription Factors , Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Moscow , Russia.
Elizaveta V
EV
Pankratova
a Department of Transcription Factors , Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Moscow , Russia.
Natalia V
NV
Soshnikova
a Department of Transcription Factors , Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Moscow , Russia.
Alexander G
AG
Stepchenko
b Department of Molecular Pharmacology and Radiobiology , Pirogov Russian National Research Medical University , Moscow , Russia.
Alexander S
AS
Dukhanin
a Department of Transcription Factors , Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Moscow , Russia.
Sofia G
SG
Georgieva
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002166:Camptothecin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004338:Drug Combinations; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D050811:Octamer Transcription Factor-1 / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D000970:Antineoplastic Agents; D004338:Drug Combinations; D050811:Octamer Transcription Factor-1; D020033:Protein Isoforms; D011965:Receptors, Glucocorticoid; D000071999:S100 Calcium-Binding Protein A4; C077591:S100A4 protein, human; D003907:Dexamethasone; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D002166:Camptothecin
Dexamethasone; Octamer transcription factor-1; S100A4; human lymphoblastoid cells; namalwa