title: WAP four-disulfide core domain protein 2 gene(WFDC2) is a target of estrogen in ovarian cancer cells.
abstract: BACKGROUND
  WAP four-disulfide core domain protein 2 (WFDC2) shows a tumor-restricted upregulated pattern of expression in ovarian cancer.
  
  
  METHODS
  We investigated the role of estradiol (E2) on cell growth in estrogen-sensitive or estrogen-insensitive ovarian cancer cell lines. Real-time (RT)-PCR and western blotting were used to examine the expression of WFDC2 at RNA and protein levels. Growth traits of cells transfected with WFDC2-shRNA or blank control were assessed using MMT arrays. Cell apoptosis was analyzed using annexin V-FITC/PI and flow cytometry. Estrogen receptor expression was evaluated using RT-PCR and flow cytometry. Apoptosis-related proteins induced by E2 directly and indirectly were determined using an antibody array comparing cells transfected with WFDC2- shRNA or a blank control.
  
  
  RESULTS
  High-dose (625 ng/ml) E2 increased the expression of WFDC2 in HO8910 cells at both the mRNA and protein levels. However, E2 had no effect on WFDC2 expression in estrogen-insensitive SKOV3 cells. Of interest, knockdown of WFDC2 enabled a considerable estrogen response in SKOV3 cells in terms of proliferation, similar to estrogen-responsive HO8910 cells. This transformation of SKOV3 cells into an estrogen-responsive phenotype was accompanied by upregulation of estrogen receptor beta (ERß) and an effect on cell apoptosis under E2 treatment by regulating genes related to cell proliferation and apoptosis.
  
  
  CONCLUSIONS
  We postulate that increased WFDC2 expression plays an important role in altering the estrogen pathway in ovarian cancer, and the identification of WFDC2 as a new player in endocrine-related cancer encourages further studies on the significance of this gene in cancer development and therapy.
authors.affiliation: School of Biotechnology, Southern Medical University, 1023 Shatainan Road, Guangzhou, 510515, China. 16403249@qq.com.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Biotechnology, Southern Medical University, 1023 Shatainan Road, Guangzhou, 510515, China. yaoc719@sina.com.
authors.forename: Suihai
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Biotechnology, Southern Medical University, 1023 Shatainan Road, Guangzhou, 510515, China. hunao19@sina.com.
authors.forename: Tiancai
authors.initials: T
authors.lastname: Liu
authors.affiliation: School of Biotechnology, Southern Medical University, 1023 Shatainan Road, Guangzhou, 510515, China. wangchenmi@sina.com.
authors.forename: Yingsong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: School of Biotechnology, Southern Medical University, 1023 Shatainan Road, Guangzhou, 510515, China. 23473820@qq.com.|Molecular Oncology Laboratories, Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. 23473820@qq.com.
authors.forename: Ji-Liang
authors.initials: JL
authors.lastname: Li
authors.affiliation: School of Biotechnology, Southern Medical University, 1023 Shatainan Road, Guangzhou, 510515, China. woailanmi@sina.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004958:Estradiol / Q000502:physiology*; D004967:Estrogens / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D004967:Estrogens; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human; D004958:Estradiol