ArticleJournal of ovarian research2016
WAP four-disulfide core domain protein 2 gene(WFDC2) is a target of estrogen in ovarian cancer cells.
Article in Journal of ovarian research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 13 citations in OpenAlex.
- Mechanistic Insights into Tumorigenesis from Serum Proteins.medRxiv : the preprint server for health sciences · 2025Article
- Article
- WFDC3 inhibits tumor metastasis by promoting the ERβ-mediated transcriptional repression of TGFBR1 in colorectal cancer.Cell death & disease · 2023Article
- Analysis of Copy-Number Variations and Feline Mammary Carcinoma Survival.Scientific reports · 2020Article
- Article
- Beyond the Biomarker: Understanding the Diverse Roles of Human Epididymis Protein 4 in the Pathogenesis of Epithelial Ovarian Cancer.Frontiers in oncology · 2018Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWAP four-disulfide core domain protein 2 (WFDC2) shows a tumor-restricted upregulated pattern of expression in ovarian cancer.
methodsWe 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.
resultsHigh-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.
conclusionsWe 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.
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