Dexamethasone downregulates expression of carbonic anhydrase IX via HIF-1α and NF-κB-dependent mechanisms
| Autor: | Katarina Laposova, Veronika Simko, Martina Takacova, Elena Ondriskova-Panisova, Jaromir Pastorek, Michaela Debreova, Silvia Pastorekova, Lucia Csaderova |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Down-Regulation dexamethasone Biology carbonic anhydrase IX 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Glucocorticoid receptor Downregulation and upregulation Antigens Neoplasm Transcription (biology) Cell Line Tumor Spheroids Cellular medicine Humans transcriptional regulation Promoter Regions Genetic Glucocorticoids Transcription factor Cell Proliferation Binding Sites hypoxia-inducible factor-1α Dose-Response Relationship Drug NF-kappa B NF-κB Articles Cell cycle Hypoxia-Inducible Factor 1 alpha Subunit NFKB1 Cell Hypoxia 030104 developmental biology Oncology chemistry nuclear factor-kappaB 030220 oncology & carcinogenesis MCF-7 Cells Cancer research Glucocorticoid medicine.drug |
| Zdroj: | International Journal of Oncology |
| ISSN: | 1791-2423 1019-6439 |
| Popis: | 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 dexa-methasone treatment and implication of additional regulatory mechanisms can be relevant for the CA IX-related clinical applications. |
| Databáze: | OpenAIRE |
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