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Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2016

Open Access 01-12-2016 | Research

WAP four-disulfide core domain protein 2 gene(WFDC2) is a target of estrogen in ovarian cancer cells

Authors: Yao Chen, Suihai Wang, Tiancai Liu, Yingsong Wu, Ji-Liang Li, Ming Li

Published in: Journal of Ovarian Research | Issue 1/2016

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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.
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Metadata
Title
WAP four-disulfide core domain protein 2 gene(WFDC2) is a target of estrogen in ovarian cancer cells
Authors
Yao Chen
Suihai Wang
Tiancai Liu
Yingsong Wu
Ji-Liang Li
Ming Li
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2016
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-015-0210-y

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