Abstract
We previously demonstrated that 14-3-3σ was downregulated in 5-fluorouracil (5-Fu)-resistant MCF-7 breast cancer cells (MCF-7/5-Fu). Here, we found that stably enhanced 14-3-3σ expression strengthened the effects of 5-Fu, Mitoxantrone and cDDP. 14-3-3σ stabilised the p53 protein and bound Akt to inhibit its activity and its downstream targets: survivin, Bcl-2 and NF-κB-p50. In addition, decreased p53 expression, but not promoter hypermethylation, was responsible for the downregulation of 14-3-3σ in MCF-7/5-Fu cells. Meanwhile, initial treatments with high concentrations of 5-Fu clearly induced 14-3-3σ and p53 expression in a time-dependent manner. 14-3-3σ-mediated molecular events that synergise with p53 may play important roles in the chemotherapy of breast cancer.
Original language | English |
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Pages (from-to) | 163-168 |
Number of pages | 6 |
Journal | FEBS Letters |
Volume | 586 |
Issue number | 2 |
DOIs | |
State | Published - 20 Jan 2012 |
Externally published | Yes |
Keywords
- 14-3-3σ
- Akt
- Breast cancer
- Drug resistance
- Methylation
- p53