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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Apoptosis, Cell Line, Tumor, Cell Proliferation, Estradiol, Estrogens, Female, Gene Expression Regulation, Neoplastic, Humans, Ovarian Neoplasms, Proteins, Signal Transduction.
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Is wAP four-disulfide core domain protein 2 gene ( WFDC2 ) a target of estrogen in ovarian cancer cells? Context: WAP four-disulfide core domain protein 2 (WFDC2) shows a tumor-restricted upregulated pattern of expression in ovarian cancer. 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. 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.
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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. Final Decision: yes