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

Guopei Zheng, Yan Xiong, Sisi Yi, Weijia Zhang, Bo Peng, Qiong Zhang, Zhimin He

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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 languageEnglish
Pages (from-to)163-168
Number of pages6
JournalFEBS Letters
Volume586
Issue number2
DOIs
StatePublished - 20 Jan 2012
Externally publishedYes

Keywords

  • 14-3-3σ
  • Akt
  • Breast cancer
  • Drug resistance
  • Methylation
  • p53

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