Abstract
PurposeOne of the hypotheses regarding the genesis of epithelial ovarian cancer involves the action of androgens on the proliferation of epithelial ovarian cells, as well as inclusion cysts. The purpose of the present study was to evaluate whether DHT causes changes in the TGF-β1 pathway that might modify the anti-proliferative effect of the latter.MethodsThe levels of TGF-β1 protein, of its receptors (TGFBR1 and TGFBR2), of Smad2/3 (canonical signaling pathway protein) and of p21 (cell cycle protein) were assessed in ovarian tissues, epithelial ovarian cancer cell lines (A2780) and control cell lines (HOSE) through the use of immunohistochemistry and immunocytochemistry. Additionally, cell lines were treated with 100 nmol/L DHT, 10 ng/mL of TGF-β1 and DHT + TGF-β1 during 72 h in the presence and absence of a siRNA against androgen receptor. After treatment, TGFBR1 and TGFBR2 levels were detected through Western blotting and p21 was assessed through immunocytochemistry.ResultsEpithelial ovarian cancer tissues showed a decrease in TGF-β1 I receptor (p < 0.05) and a change in Smad2/3 protein levels. Additionally, after treatment of cell lines with DHT, protein levels of TGF-β1 receptors (TGFBR1–TGFBR2) showed a decrease (p < 0.05) that might cause a potential disorder in TGF-β1 response, represented by the significant decrease in p21 protein levels in the presence of DHT (p < 0.001).ConclusionsOverall, our results indicate a defect in the canonical TGF-β signaling pathway in epithelial ovarian cancer caused by androgen action, thus suggesting eventual changes in such tissue proliferation rates.
Highlights
Epithelial ovarian cancer (EOC) accounts for 85–95 % of ovarian malignant neoplasms (Auersperg 2013)
Overall, our results indicate a defect in the canonical TGF-β signaling pathway in epithelial ovarian cancer caused by androgen action, suggesting eventual changes in such tissue proliferation rates
In order to address this issue, the present research examined protein levels of the molecules implicated in the TGF-β signaling pathway such as TGF-β, its receptors and Smad2/3 proteins in tissues from patients with EOC and in ovarian cell lines
Summary
Epithelial ovarian cancer (EOC) accounts for 85–95 % of ovarian malignant neoplasms (Auersperg 2013). According to a recent FIGO report, EOC is the seventh most common disease among women worldwide (Prat 2007). Women with EOC have a low survival rate (Jordan et al 2006; Auersperg et al 2002). The pathogenesis of ovarian carcinoma is somewhat unclear, and several mechanisms have been suggested to explain the etiology of such disease (Lukanova and Kaaks 2005). In such context, among the hypotheses attempting to explain its origin, there is one related to steroid hormones, proposing that excess stimulation of ovarian surface epithelium with androgens might
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