Inactivation of the FoxO3a transcription factor is associated with the production of reactive oxygen species during protein kinase CK2 downregulation-mediated senescence in human colon cancer and breast cancer cells
| Autor: | Young-Seuk Bae, Seong-Yeol Park |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Senescence Colon Active Transport Cell Nucleus Biophysics Down-Regulation Breast Neoplasms Biology Biochemistry 03 medical and health sciences Downregulation and upregulation Humans Breast Casein Kinase II Molecular Biology Transcription factor Cellular Senescence PI3K/AKT/mTOR pathway chemistry.chemical_classification Reactive oxygen species Gene knockdown 030102 biochemistry & molecular biology Forkhead Box Protein O3 Cell Biology HCT116 Cells Molecular biology Up-Regulation Cell biology Gene Expression Regulation Neoplastic 030104 developmental biology chemistry Colonic Neoplasms MCF-7 Cells Phosphorylation Female Casein kinase 2 Reactive Oxygen Species Proto-Oncogene Proteins c-akt |
| Zdroj: | Biochemical and Biophysical Research Communications. 478:18-24 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2016.07.106 |
| Popis: | We previously showed that protein kinase CK2 downregulation mediates senescence through the reactive oxygen species (ROS)-p53-p21(Cip1/WAF1) pathway in various human cells. In the present study, we investigated whether the FoxO3a transcription factor is associated with ROS production during CK2 downregulation-induced senescence in human colon cancer HCT116 and breast cancer MCF-7 cells. FoxO3a overexpression suppressed ROS production and p53 stabilization induced by a CK2α knockdown. CK2α downregulation induced nuclear export of FoxO3a through stimulation of AKT-mediated phosphorylation of FoxO3a and decreased transcription of its target genes (Cu/ZnSOD, MnSOD, and catalase). In contrast, CK2α overexpression inhibited AKT-mediated FoxO3a phosphorylation. This resulted in nuclear accumulation of FoxO3a, and elevated expression of its target genes. Therefore, these data indicate for the first time that CK2 downregulation stimulates ROS generation by inhibiting FoxO3a during premature senescence in human colon and breast cancer cells. |
| Databáze: | OpenAIRE |
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