Conclusions
Overall, 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.
Methods
The 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.
Purpose
One 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.
Results
Epithelial 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). Conclusions: Overall, 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.