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14‐3‐3σ regulation by p53 mediates a chemotherapy response to 5‐fluorouracil in MCF‐7 breast cancer cells via Akt inactivation
Author(s) -
Zheng Guopei,
Xiong Yan,
Yi Sisi,
Zhang Weijia,
Peng Bo,
Zhang Qiong,
He Zhimin
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.11.034
Subject(s) - survivin , downregulation and upregulation , mcf 7 , cancer research , breast cancer , fluorouracil , chemotherapy , mitoxantrone , protein kinase b , apoptosis , chemistry , cancer , biology , medicine , gene , human breast , biochemistry
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.