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FEBS Lett. 2012 Jan 20;586(2):163-8. doi: 10.1016/j.febslet.2011.11.034. Epub 2011 Dec 16.

14-3-3σ regulation by p53 mediates a chemotherapy response to 5-fluorouracil in MCF-7 breast cancer cells via Akt inactivation.

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1
Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan, PR China.

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.

PMID:
22192357
DOI:
10.1016/j.febslet.2011.11.034
[Indexed for MEDLINE]
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