title: Biological role and prognostic significance of NAC1 in ovarian cancer.
abstract: OBJECTIVE
  This study examined the biological and clinical significance of NAC1 expression in ovarian cancer and assessed whether NAC1 has the potential to be a therapeutic target.
  
  
  METHODS
  NAC1 expression and gene amplification were assessed in ovarian cancers by immunohistochemistry, fluorescence in situ hybridization, and clinical data collected by a retrospective chart review. NAC1 gene knockdown using silencing RNA and a NAC1 gene transfection system were used to assess NAC1 function in ovarian cancer tissue samples.
  
  
  RESULTS
  The frequency of positive NAC1 expression in serous adenocarcinomas (50.0%:22/44) was significantly higher than that in the other histological subtypes (33.3%: 10/30). NAC1 gene amplification was identified in seven (9.5%) of 74 ovarian carcinomas. Positive NAC1 expression significantly correlated with shorter disease-free and overall survival (P = 0.002, P = 0.0048). A multivariate analysis showed that positive NAC1 expression was an independent prognostic factor for disease-free and overall survival after standard platinum-taxane chemotherapy (P = 0.0027, P = 0.0302). Profound growth inhibition, increased apoptosis, decreased cell proliferation, and decreased cell migration and invasion were observed in silencing RNA-treated cancer cells with NAC1 overexpression compared with cancer cells without NAC1 expression. NAC1 overexpression stimulated proliferation, migration, and invasion in ovarian cancer cell lines KF28 and TOV-21G, which normally lacked NAC1 expression.
  
  
  CONCLUSIONS
  These findings indicate that NAC1 over-expression is critical to the growth and survival of ovarian cancers. Furthermore, they suggest that NAC1 silencing RNA-induced phenotypes depend on the expression status of the targeted cell line. Therefore, NAC1-targeted therapy may benefit ovarian cancer patients with NAC1 expression.
authors.affiliation: Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Shimane, Japan. kn88@med.shimane-u.ac.jp
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nakayama
authors.forename: Mohammed Tanjimur
authors.initials: MT
authors.lastname: Rahman
authors.forename: Munmun
authors.initials: M
authors.lastname: Rahman
authors.forename: Shamima
authors.initials: S
authors.lastname: Yeasmin
authors.forename: Masako
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Atsuko
authors.initials: A
authors.lastname: Katagiri
authors.forename: Kouji
authors.initials: K
authors.lastname: Iida
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakayama
authors.forename: Kohji
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D055785:Gene Knockdown Techniques; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000099186:Histone Deacetylase 3
chemical_list: D014408:Biomarkers, Tumor; D006655:Histone Deacetylases; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D000099186:Histone Deacetylase 3; C516477:NACC1 protein, human; C400300:HDAC4 protein, human