title: Germ cell specific protein VASA is over-expressed in epithelial ovarian cancer and disrupts DNA damage-induced G2 checkpoint.
abstract: OBJECTIVE
  Cancer cells have characteristics, such as high telomerase activity and high levels of migration activity and proliferation, which are very similar to those of germ cell lineages. In this study, we examined the expression of VASA, a germ cell lineage specific marker and evaluated its clinical significance in epithelial ovarian cancer (EOC).
  
  
  METHODS
  We investigated VASA expression in 75 EOC tissues by immunohistochemistry, correlating results with clinicopathological factors. To clarify the effects of VASA on cellular phenotypes, we compared the protein expression profiles between SKOV-3 cells stably expressing VASA (SKOV-3-VASA) and vector-control cell lines by coupling 2D fingerprinting and identification of proteins by mass spectrometry.
  
  
  RESULTS
  VASA expression in tumor cells was found in 21 of 75 cases and was positively correlated with high age and serous histology. Significant down-regulation of 14-3-3sigma was observed in SKOV-3-VASA versus control cells. Over-expression of VASA abrogates the G2 checkpoint, induced by DNA damage, by down-regulating the expression of 14-3-3sigma.
  
  
  CONCLUSIONS
  These results suggest that VASA may either play a direct role in the progression of EOC or serve as a valuable marker of tumorigenesis.
authors.affiliation: Section of Translational Research, Hyogo Cancer Center, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sudo
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Mikami
authors.forename: Mieko
authors.initials: M
authors.lastname: Otani
authors.forename: Masaoki
authors.initials: M
authors.lastname: Takano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itamochi
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Katabuchi
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ito
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Nishimura
mesh_terms: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis* / Q000235:genetics; D004249:DNA Damage / Q000502:physiology*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000473:pathology; D005092:Exonucleases / Q000096:biosynthesis / Q000235:genetics; D005095:Exoribonucleases; D005260:Female; D016195:G2 Phase / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; C498288:DDX4 protein, human; D053487:DEAD-box RNA Helicases