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The Involvement of RhoA and Wnt-5a in the Tumorigenesis and Progression of Ovarian Epithelial Carcinoma
Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
Department of Gynecology, the General Hospital of Shenyang Military Region, Shenyang 110045, China
Department of Biochemistry and Molecular Biology, Institute of Pathology and Pathophysiology, College of Basic Medicine, China Medical University, Shenyang 110001, China
Clinical Cancer Institute, Kanagawa Cancer Center, Yokohama 241-0815, Japan
* Author to whom correspondence should be addressed.
Received: 29 August 2013; in revised form: 26 November 2013 / Accepted: 3 December 2013 / Published: 12 December 2013
Abstract: Background: Ras homolog gene family member A (RhoA) is involved in Wnt-5a–induced migration of gastric and breast cancer cells. We investigated the roles of RhoA and Wnt-5a in ovarian carcinoma. Methods: RhoA and Wnt-5a mRNA and protein expression in normal fallopian tube epithelium, benign tumors, primary ovarian carcinomas, and metastatic omentum were quantified. RhoA or Wnt-5a was knocked down in OVCAR3 ovarian carcinoma cells using siRNAs and cell phenotype and expression of relevant molecules were assayed. Results: RhoA and Wnt-5a mRNA and protein expression were found to be significantly higher in metastatic omentum than in ovarian carcinomas, benign tumors, and normal fallopian tube epithelium (p < 0.05), and positively associated with differentiation and FIGO staging (stage I/II vs. stage III/IV) in ovarian carcinoma (p < 0.05). RhoA and Wnt-5a expression were positively correlated in ovarian carcinoma (p = 0.001, R2 = 0.1669). RhoA or Wnt-5a knockdown downregulated RhoA and Wnt-5a expression; reduced cell proliferation; promoted G1 arrest and apoptosis; suppressed lamellipodia formation, cell migration, and invasion; and reduced PI3K, Akt, p70S6k, Bcl-xL, survivin, and VEGF mRNA or protein expression. Conclusions: This is the first demonstration that RhoA and Wnt-5a are associated with ovarian carcinogenesis and apoptosis inhibition; there might be positive correlation between RhoA and Wnt-5a expression. RhoA is a potential tumorigenesis, differentiation, and progression biomarker in ovarian carcinoma.
Keywords: ovarian carcinoma; RhoA; Wnt-5a signaling; tumorigenesis and progression; phenotype
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Chen, S.; Wang, J.; Gou, W.-F.; Xiu, Y.-L.; Zheng, H.-C.; Zong, Z.-H.; Takano, Y.; Zhao, Y. The Involvement of RhoA and Wnt-5a in the Tumorigenesis and Progression of Ovarian Epithelial Carcinoma. Int. J. Mol. Sci. 2013, 14, 24187-24199.
Chen S, Wang J, Gou W-F, Xiu Y-L, Zheng H-C, Zong Z-H, Takano Y, Zhao Y. The Involvement of RhoA and Wnt-5a in the Tumorigenesis and Progression of Ovarian Epithelial Carcinoma. International Journal of Molecular Sciences. 2013; 14(12):24187-24199.
Chen, Shuo; Wang, Jun; Gou, Wen-Feng; Xiu, Ying-Ling; Zheng, Hua-Chuan; Zong, Zhi-Hong; Takano, Yasuo; Zhao, Yang. 2013. "The Involvement of RhoA and Wnt-5a in the Tumorigenesis and Progression of Ovarian Epithelial Carcinoma." Int. J. Mol. Sci. 14, no. 12: 24187-24199.