title: Aberrant expression of EZH2 is associated with pathological findings and P53 alteration.
abstract: OBJECTIVE
  Enhancer of zeste homolog-2 (EZH2) and B lymphoma Mo-MLV insertion region-1 homolog (BMI1) are members of the polycomb group of proteins, which function as transcriptional repressors through chromatin modification. EZH2 forms part of the polycomb repressive complex (PRC)-2, while BMI1 is a component of PRC1. Previous studies have shown that EZH2 is highly expressed in various type of cancers. Expression of EZH2 is reported to be regulated by the P53-E2F/retinoblastoma (RB)-related pathway, and a correlation between P53 mutation and EZH2 expression was recently found in breast cancer. Here, we examined the relationship between P53 and EZH2 in oral squamous cell carcinoma (OSCC).
  
  
  METHODS
  Using immunohistochemistry, we investigated the expression of EZH2 and BMI1 in 99 surgically-resected OSCC and 34 epithelial dysplasia samples. We analyzed associations between aberrant expression of EZH2 and BMI1, and clinicopathological findings and patient outcome. P53 expression was also examined and analyzed in relation to EZH2 and BMI1 expression.
  
  
  RESULTS
  EZH2 and BMI1 protein were up-regulated in OSCC tissues compared with epithelial dysplasia and normal epithelium. Aberrant EZH2 and BMI1 protein expression was observed in 32 and 59 of the 99 OSCC samples, respectively. Aberrant EZH2 and BMI1 expression was significantly associated with mode of invasion, but not with lymph node metastasis or survival rate. Aberrant EZH2 expression was associated with P53 alteration in OSCC tissue. Expression of EZH2 mRNA in SAS/neo cells, which have wild-type P53, was significantly lower than in SAS/mp53 cells that have a mutant P53 gene.
  
  
  CONCLUSIONS
  P53 alteration may be involved in dysregulated EZH2 expression, and aberrant expression of EZH2 may play a role in carcinogenesis of OSCC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan. shintani@dent.showa-u.ac.jp.
authors.forename: Sunao
authors.initials: S
authors.lastname: Shiogama
authors.forename: Sayaka
authors.initials: S
authors.lastname: Yoshiba
authors.forename: Daisuke
authors.initials: D
authors.lastname: Soga
authors.forename: Hiromi
authors.initials: H
authors.lastname: Motohashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Shintani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D018572:Disease-Free Survival; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009154:Mutation; D009361:Neoplasm Invasiveness; D063150:Polycomb Repressive Complex 1 / Q000235:genetics* / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C069077:BMI1 protein, human; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1
keywords: BMI1; EZH2; human oral squamous cell carcinoma; p53