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Int. J. Mol. Sci. 2013, 14(12), 24187-24199; doi:10.3390/ijms141224187
Article

The Involvement of RhoA and Wnt-5a in the Tumorigenesis and Progression of Ovarian Epithelial Carcinoma

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1 Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China 2 Department of Gynecology, the General Hospital of Shenyang Military Region, Shenyang 110045, China 3 Department of Biochemistry and Molecular Biology, Institute of Pathology and Pathophysiology, College of Basic Medicine, China Medical University, Shenyang 110001, China 4 Clinical Cancer Institute, Kanagawa Cancer Center, Yokohama 241-0815, Japan
* Author to whom correspondence should be addressed.
Received: 29 August 2013 / Revised: 26 November 2013 / Accepted: 3 December 2013 / Published: 12 December 2013
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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 ovarian carcinoma; RhoA; Wnt-5a signaling; tumorigenesis and progression; phenotype
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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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.

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