title: 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.
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Gou
authors.forename: Ying-Ling
authors.initials: YL
authors.lastname: Xiu
authors.forename: Hua-Chuan
authors.initials: HC
authors.lastname: Zheng
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Zong
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
authors.affiliation: Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China. yida.zhaoyang@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis; D063646:Carcinogenesis; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D020742:rhoA GTP-Binding Protein