title: 14-3-3σ regulation by p53 mediates a chemotherapy response to 5-fluorouracil in MCF-7 breast cancer cells via Akt inactivation.
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.
authors.affiliation: Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan, PR China.
authors.forename: Guopei
authors.initials: G
authors.lastname: Zheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiong
authors.forename: Sisi
authors.initials: S
authors.lastname: Yi
authors.forename: Weijia
authors.initials: W
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: He
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects; D005092:Exonucleases / Q000235:genetics* / Q000378:metabolism; D005095:Exoribonucleases; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*
chemical_list: D048948:14-3-3 Proteins; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051058:Oncogene Protein v-akt; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; D005472:Fluorouracil