title: Wnt5a as a predictor in poor clinical outcome of patients and a mediator in chemoresistance of ovarian cancer.
abstract: BACKGROUND
  Wnt5a regulates numerous signaling pathways controlling a wide range of cellular processes, including cell proliferation, differentiation, and apoptosis. However, it is still unclear whether Wnt5a is involved in mediating chemoresistance in cancer. We studied the correlation of Wnt5a expression with clinicopathologic parameters and survival in epithelial ovarian cancer and the effect of Wnt5a expression on chemoresistance of ovarian cancer cells.
  
  
  METHODS
  Wnt5a expression was immunohistochemically examined in ovarian cancer, benign tumor, and normal ovarian tissues. Two stable cell lines were established, namely, SKOV3/Wnt5a, which overexpressed Wnt5a, and SKOV3/miRNA, which downregulated Wnt5a expression using microRNA (miRNA). Wnt5a expression level was evaluated by semiquantitative reverse transcription-polymerase chain reaction, Western blot analysis, and immunofluorescence assay. The sensitivity of all transfected and untransfected cell lines to chemotherapeutic drugs (paclitaxel, oxaliplatin, 5-fluorouracil, epirubicin, and etoposide) was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay.
  
  
  RESULTS
  Wnt5a was found to be significantly higher in ovarian cancer compared with benign tumors and normal ovaries. High levels of Wnt5a expression were associated with the International Federation of Gynecology and Obstetrics stage and significantly predicted a poorer overall survival and progression-free survival compared with low Wnt5a expression. In addition, Wnt5a overexpression in SKOV3/Wnt5a cells decreased chemosensitivity compared with normal and empty vector controls (P < 0.05). Alternatively, Wnt5a down-regulation in SKOV3/miRNA cells led to a significant increase in chemosensitivity (P < 0.05).
  
  
  CONCLUSIONS
  Wnt5a immunoreactivity may be a useful prognostic indicator in patients with ovarian cancer. These results clarified for the first time the possibility that Wnt5a plays an important role in regulating chemosensitivity to anticancer drugs in ovarian cancer cells.
authors.affiliation: Department of Obstetrics and Gynecology, Harbin Medical University, Heilongjiang, People's Republic of China.
authors.forename: Chunjie
authors.initials: C
authors.lastname: Peng
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhang
authors.forename: Hongli
authors.initials: H
authors.lastname: Yu
authors.forename: Donglai
authors.initials: D
authors.lastname: Wu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zheng
mesh_terms: D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D010053:Ovary / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D000071818:Wnt-5a Protein
chemical_list: D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein