Germ cell specific protein VASA is over-expressed in epithelial ovarian cancer and disrupts DNA damage-induced G2 checkpoint.
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.
Hashimoto
Hisashi
H
Section of Translational Research, Hyogo Cancer Center, Japan.
Sudo
Tamotsu
T
Mikami
Yoshiki
Y
Otani
Mieko
M
Takano
Masaoki
M
Tsuda
Hiroshi
H
Itamochi
Hiroaki
H
Katabuchi
Hidetaka
H
Ito
Masaharu
M
Nishimura
Ryuichiro
R
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
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