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.
DOI
10.1186/s13048-015-0210-y
Publication Date
2016-02-29
Publication Title
Journal of Ovarian Research
Volume
9
Issue
1
Publisher
Springer Science and Business Media LLC
ISSN
1757-2215
Embargo Period
2024-11-19
Recommended Citation
Chen, Y., Wang, S., Liu, T., & et al. (2016) 'WAP four-disulfide core domain protein 2 gene(WFDC2) is a target of estrogen in ovarian cancer cells', Journal of Ovarian Research, 9(1). Springer Science and Business Media LLC: Available at: https://doi.org/10.1186/s13048-015-0210-y
