title: 14-3-3sigma-dependent resistance to cisplatin.
abstract: BACKGROUND
  A major factor that impedes the clinical success of cisplatin-based chemotherapy for cancer is cisplatin resistance by cancer cells.
  
  
  METHODS
  The sensitivity of parental HCT116 human colon cancer cell line and its isogenic gene-knockout sub-lines to cisplatin was determined by clonogenicity assay; furthermore, p53 activation, p21 expression, cell cycle arrest and senescence in these cells after cisplatin treatment were investigated.
  
  
  RESULTS
  Parental cells were six times more resistant than 14-3-3sigma-knockout (sigma-KO) cells to cisplatin. Moreover, activation of p53, p53-dependent expression of p21 and p21-dependent senescence were observed in sigma-KO, but not parental cells after a treatment with a low cisplatin dose.
  
  
  CONCLUSIONS
  A 14-3-3sigma-dependent mechanism inhibits p53 activation in parental cells treated with a low cisplatin dose, thereby blocking p21 expression that is essential for senescence and consequently conferring to the parental cells a significant degree of resistance to cisplatin.
authors.affiliation: Department of Preclinical Sciences, New York College of Podiatric Medicine, New York, NY 10035, U.S.A. zhan@nycpm.edu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Han
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Dimas
authors.forename: Xuefei
authors.initials: X
authors.lastname: Tian
authors.forename: Yongbao
authors.initials: Y
authors.lastname: Wang
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Hemmi
authors.forename: Kanae
authors.initials: K
authors.lastname: Yamada
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kato
authors.forename: Panayotis
authors.initials: P
authors.lastname: Pantazis
authors.forename: Rama J
authors.initials: RJ
authors.lastname: Ramanujam
authors.forename: Shrikant
authors.initials: S
authors.lastname: Anant
authors.forename: James H
authors.initials: JH
authors.lastname: Wyche
authors.forename: Courtney W
authors.initials: CW
authors.lastname: Houchen
mesh_terms: D048948:14-3-3 Proteins; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D016922:Cellular Senescence / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D005092:Exonucleases / Q000235:genetics / Q000378:metabolism*; D005095:Exoribonucleases; D005434:Flow Cytometry; D055786:Gene Knockout Techniques; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D048948:14-3-3 Proteins; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009363:Neoplasm Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; D002945:Cisplatin