title: Role of dihydrotestosterone (DHT) on TGF-β1 signaling pathway in epithelial ovarian cancer cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Laboratory of Endocrinology and Reproductive Biology, University of Chile Clinical Hospital, Avda. Santos Dumont # 999, Independencia, Santiago, Chile.
authors.forename: Karla
authors.initials: K
authors.lastname: Kohan-Ivani
authors.affiliation: Department of Pathology, School of Medicine, San Borja Arriarán Clinical Hospital, University of Chile, Santiago, Chile.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gabler
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, University of Chile Clinical Hospital, Santiago, Chile.
authors.forename: Alberto
authors.initials: A
authors.lastname: Selman
authors.affiliation: Laboratory of Endocrinology and Reproductive Biology, University of Chile Clinical Hospital, Avda. Santos Dumont # 999, Independencia, Santiago, Chile.|Department of Obstetrics and Gynecology, School of Medicine, University of Chile Clinical Hospital, Santiago, Chile.
authors.forename: Margarita
authors.initials: M
authors.lastname: Vega
authors.affiliation: Laboratory of Endocrinology and Reproductive Biology, University of Chile Clinical Hospital, Avda. Santos Dumont # 999, Independencia, Santiago, Chile. cromero@hcuch.cl.|Department of Obstetrics and Gynecology, School of Medicine, University of Chile Clinical Hospital, Santiago, Chile. cromero@hcuch.cl.|Advanced Center for Chronic Diseases (ACCDiS), School of Medicine, University of Chile, Santiago, Chile. cromero@hcuch.cl.
authors.forename: Carmen
authors.initials: C
authors.lastname: Romero
mesh_terms: D000728:Androgens / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D000077216:Carcinoma, Ovarian Epithelial; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C410798:AR protein, human; D000728:Androgens; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D011944:Receptors, Androgen; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1; D013196:Dihydrotestosterone; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625841:TGFBR1 protein, human
keywords: Androgen receptor; Epithelial ovarian cancer; TGF-β signaling pathway