The involvement of RhoA and Wnt-5a in the tumorigenesis and progression of ovarian epithelial carcinoma.

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.

journal_name

Int J Mol Sci

authors

Chen S,Wang J,Gou WF,Xiu YL,Zheng HC,Zong ZH,Takano Y,Zhao Y

doi

10.3390/ijms141224187

subject

Has Abstract

pub_date

2013-12-12 00:00:00

pages

24187-99

issue

12

issn

1422-0067

pii

ijms141224187

journal_volume

14

pub_type

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