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Article Open Access

Dexamethasone downregulates expression of carbonic anhydrase IX via HIF-1α and NF-κB-dependent mechanisms

  • Authors:
    • Veronika Simko
    • Martina Takacova
    • Michaela Debreova
    • Katarina Laposova
    • Elena Ondriskova-Panisova
    • Silvia Pastorekova
    • Lucia Csaderova
    • Jaromir Pastorek
  • View Affiliations / Copyright

    Affiliations: Institute of Virology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic
    Copyright: © Simko et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1277-1288
    |
    Published online on: July 14, 2016
       https://doi.org/10.3892/ijo.2016.3621
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Abstract

Dexamethasone is a synthetic glucocorticoid frequently used to suppress side-effects of anticancer chemotherapy. In the present study, we showed that dexamethasone treatment leads to concentration-dependent downregulation of cancer-associated marker, carbonic anhydrase IX (CA IX), at the level of promoter activity, mRNA and protein expression in 2D and 3D cancer cell models. The effect of dexamethasone on CA IX expression under hypoxic conditions is predominantly mediated by impaired transcriptional activity and decreased protein level of the main hypoxic transcription factor HIF-1α. In addition, CA9 downregulation can be caused by protein-protein interactions between activated glucocorticoid receptors, major effectors of glucocorticoid action, and transcription factors that trigger CA9 transcription (e.g. AP-1). Moreover, we identified a potential NF-κB binding site in the CA9 promoter and propose the involvement of NF-κB in the dexamethasone-mediated inhibition of CA9 transcription. As high level of CA IX is often linked to aggressive tumor behavior, poor prognosis and chemo- and radiotherapy resistance, uncovering its reduction after dexamethasone treatment and implication of additional regulatory mechanisms can be relevant for the CA IX-related clinical applications.
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Copy and paste a formatted citation
Spandidos Publications style
Simko V, Takacova M, Debreova M, Laposova K, Ondriskova-Panisova E, Pastorekova S, Csaderova L and Pastorek J: Dexamethasone downregulates expression of carbonic anhydrase IX via HIF-1α and NF-κB-dependent mechanisms. Int J Oncol 49: 1277-1288, 2016.
APA
Simko, V., Takacova, M., Debreova, M., Laposova, K., Ondriskova-Panisova, E., Pastorekova, S. ... Pastorek, J. (2016). Dexamethasone downregulates expression of carbonic anhydrase IX via HIF-1α and NF-κB-dependent mechanisms. International Journal of Oncology, 49, 1277-1288. https://doi.org/10.3892/ijo.2016.3621
MLA
Simko, V., Takacova, M., Debreova, M., Laposova, K., Ondriskova-Panisova, E., Pastorekova, S., Csaderova, L., Pastorek, J."Dexamethasone downregulates expression of carbonic anhydrase IX via HIF-1α and NF-κB-dependent mechanisms". International Journal of Oncology 49.4 (2016): 1277-1288.
Chicago
Simko, V., Takacova, M., Debreova, M., Laposova, K., Ondriskova-Panisova, E., Pastorekova, S., Csaderova, L., Pastorek, J."Dexamethasone downregulates expression of carbonic anhydrase IX via HIF-1α and NF-κB-dependent mechanisms". International Journal of Oncology 49, no. 4 (2016): 1277-1288. https://doi.org/10.3892/ijo.2016.3621
Copy and paste a formatted citation
x
Spandidos Publications style
Simko V, Takacova M, Debreova M, Laposova K, Ondriskova-Panisova E, Pastorekova S, Csaderova L and Pastorek J: Dexamethasone downregulates expression of carbonic anhydrase IX via HIF-1α and NF-κB-dependent mechanisms. Int J Oncol 49: 1277-1288, 2016.
APA
Simko, V., Takacova, M., Debreova, M., Laposova, K., Ondriskova-Panisova, E., Pastorekova, S. ... Pastorek, J. (2016). Dexamethasone downregulates expression of carbonic anhydrase IX via HIF-1α and NF-κB-dependent mechanisms. International Journal of Oncology, 49, 1277-1288. https://doi.org/10.3892/ijo.2016.3621
MLA
Simko, V., Takacova, M., Debreova, M., Laposova, K., Ondriskova-Panisova, E., Pastorekova, S., Csaderova, L., Pastorek, J."Dexamethasone downregulates expression of carbonic anhydrase IX via HIF-1α and NF-κB-dependent mechanisms". International Journal of Oncology 49.4 (2016): 1277-1288.
Chicago
Simko, V., Takacova, M., Debreova, M., Laposova, K., Ondriskova-Panisova, E., Pastorekova, S., Csaderova, L., Pastorek, J."Dexamethasone downregulates expression of carbonic anhydrase IX via HIF-1α and NF-κB-dependent mechanisms". International Journal of Oncology 49, no. 4 (2016): 1277-1288. https://doi.org/10.3892/ijo.2016.3621
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