Germ cell specific protein VASA is over-expressed in epithelial ovarian cancer and disrupts DNA damage-induced G2 checkpoint

被引：33

作者：

Hashimoto, Hisashi ^{[2
]}

Sudo, Tamotsu ^{[1
,2
]}

Mikami, Yoshiki ^{[3
]}

Otani, Mieko ^{[4
]}

Takano, Masaoki ^{[4
]}

Tsuda, Hiroshi ^{[5
]}

Itamochi, Hiroaki ^{[6
]}

Katabuchi, Hidetaka ^{[7
]}

Ito, Masaharu ^{[8
]}

Nishimura, Ryuichiro ^{[1
,2
]}

机构：

[1] Hyogo Canc Ctr, Dept Gynecol Oncol, Akashi, Hyogo 6738558, Japan

[2] Hyogo Canc Ctr, Sect Translat Res, Akashi, Hyogo 6738558, Japan

[3] Kyoto Univ Hosp, Dept Diagnost Pathol, Kyoto, Japan

[4] Kobe Gakuin Univ, Fac Pharmaceut Sci, Kobe, Hyogo, Japan

[5] Osaka City Gen Hosp, Osaka, Japan

[6] Tottori Univ, Sch Med, Dept Obstet & Gynecol, Tottori, Japan

[7] Kumamoto Univ, Sch Med, Fac Med & Pharmaceut Sci, Dept Gynecol, Kumamoto 860, Japan

[8] Ehime Univ, Sch Med, Dept Obstet & Gynecol, Matsuyama, Ehime 790, Japan

来源：

GYNECOLOGIC ONCOLOGY | 2008年 / 111卷 / 02期

关键词：

14-3-3; sigma; Ovarian cancer; VASA;

D O I：

10.1016/j.ygyno.2008.08.014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 14-3-3 sigma was observed in SKOV-3-VASA versus control cells. Over-expression of VASA abrogates the G2 checkpoint, induced by DNA damage, by down-regulation the expression of 14-3-3 sigma. 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. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：312 / 319

页数：8

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