title: Possible involvement of CCT5, RGS3, and YKT6 genes up-regulated in p53-mutated tumors in resistance to docetaxel in human breast cancers.
abstract: BACKGROUND
  Present study was aimed to investigate the relationship of p53 mutation status with response to docetaxel in breast cancers. In addition, attempts were made to identify the genes differentially expressed between p53-wild and p53-mutated breast tumors and to study their relationship with response to docetaxel.
  
  
  METHODS
  Mutational analysis of p53 was done in 50 breast tumor samples obtained from primary breast cancer patients (n = 33) and locally recurrent breast cancer patients (n = 17) before docetaxel therapy. Response to docetaxel was evaluated clinically. Gene expression profiling (n = 2,412) was conducted by adapter-tagged competitive-PCR in 186 tumor samples, which were also analyzed in their p53 mutational status in order to identify the differentially expressed genes according to p53 mutation status and their relationship with response to docetaxel.
  
  
  RESULTS
  Response rate of p53-mutated tumors (44%) was lower than that of p53-wild tumors (62%) though there was no statistical significance (P = 0.23). Of 2412 genes, mRNA expression of 13 genes was significantly different between p53-wild and p53-mutated tumors. Of these 13 genes, mRNA expression of CCT5, RGS3, and YKT6 was significantly up-regulated in p53-mutated tumors and associated with a low response rate to docetaxel. Treatment of MCF-7 cells with siRNA specific for CCT5, RGS3, or YKT6 resulted in a significant enhancement of docetaxel-induced apoptosis.
  
  
  CONCLUSIONS
  CCT5, RGS3, and YKT6 mRNA expressions, which are up-regulated in p53-mutated breast tumors, might be implicated in resistance to docetaxel and clinically useful in identifying the subset of breast cancer patients who may or may not benefit from docetaxel treatment.
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Ooe
authors.forename: Kikuya
authors.initials: K
authors.lastname: Kato
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002460:Cell Line; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins; D017024:Chemotherapy, Adjuvant; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020868:Gene Silencing / Q000187:drug effects; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D050683:R-SNARE Proteins / Q000378:metabolism; D020710:RGS Proteins; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C533301:CCT5 protein, human; D004273:DNA, Neoplasm; D020690:GTPase-Activating Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D050683:R-SNARE Proteins; D020710:RGS Proteins; C485898:RGS3 protein, human; D034741:RNA, Small Interfering; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; C491482:YKT6 protein, human; D000077143:Docetaxel; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins; D019204:GTP-Binding Proteins