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- Title
14-3-3σ regulation by p53 mediates a chemotherapy response to 5-fluorouracil in MCF-7 breast cancer cells via Akt inactivation
- Authors
Zheng, Guopei; Xiong, Yan; Yi, Sisi; Zhang, Weijia; Peng, Bo; Zhang, Qiong; He, Zhimin
- Abstract
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.
- Subjects
BREAST cancer treatment; FLUOROURACIL; CANCER chemotherapy; MITOXANTRONE hydrochloride; GENE expression; METHYLATION; PROMOTERS (Genetics)
- Publication
FEBS Letters, 2012, Vol 586, Issue 2, p163
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2011.11.034