title: Overexpression of YWHAZ relates to tumor cell proliferation and malignant outcome of gastric carcinoma.
abstract: BACKGROUND
  Several studies have demonstrated that YWHAZ (14-3-3ζ), included in the 14-3-3 family of proteins, has been implicated in the initiation and progression of cancers. We tested whether YWHAZ acted as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC).
  
  
  METHODS
  We analysed 7 GC cell lines and 141 primary tumours, which were curatively resected in our hospital between 2001 and 2003.
  
  
  RESULTS
  Overexpression of the YWHAZ protein was frequently detected in GC cell lines (six out of seven lines, 85.7%) and primary tumour samples of GC (72 out of 141 cases, 51%), and significantly correlated with larger tumour size, venous and lymphatic invasion, deeper tumour depth, and higher pathological stage and recurrence rate. Patients with YWHAZ-overexpressing tumours had worse overall survival rates than those with non-expressing tumours in both intensity and proportion expression-dependent manner. YWHAZ positivity was independently associated with a worse outcome in multivariate analysis (P=0.0491, hazard ratio 2.3 (1.003-5.304)). Knockdown of YWHAZ expression using several specific siRNAs inhibited the proliferation, migration, and invasion of YWHAZ-overexpressing GC cells. Higher expression of the YWHAZ protein was significantly associated with the lower expression of miR-375 in primary GC tissues (P=0.0047).
  
  
  CONCLUSIONS
  These findings suggest that YWHAZ has a pivotal role in tumour cell proliferation through its overexpression, and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors: Y
authors: Y
authors: Nishimura
authors: S
authors: S
authors: Komatsu
authors: D
authors: D
authors: Ichikawa
authors: H
authors: H
authors: Nagata
authors: S
authors: S
authors: Hirajima
authors: H
authors: H
authors: Takeshita
authors: T
authors: T
authors: Kawaguchi
authors: T
authors: T
authors: Arita
authors: H
authors: H
authors: Konishi
authors: K
authors: K
authors: Kashimoto
authors: A
authors: A
authors: Shiozaki
authors: H
authors: H
authors: Fujiwara
authors: K
authors: K
authors: Okamoto
authors: H
authors: H
authors: Tsuda
authors: E
authors: E
authors: Otsuji
mesh_terms: D048948:14-3-3 Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C572235:YWHAZ protein, human